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(Circulation. 1997;96:1071-1073.)
© 1997 American Heart Association, Inc.

Articles

Regional Variations of Blood Pressure

Environment or Genes?

Theodore A. Kotchen, MD; ; Jane Morley Kotchen, MD, MPH

From the Departments of Medicine and Epidemiology, Medical College of Wisconsin, Milwaukee.

Correspondence to Theodore A. Kotchen, MD, Professor and Chairman, Department of Medicine, Medical College of Wisconsin, 9200 W Wisconsin Ave, Milwaukee, WI 53226.

Key Words: Editorials • blood pressure • diet • genetics • hypertension

	Introduction

Top Introduction References

 
According to data obtained from cross-sectional surveys, only minor and inconsistent regional differences in hypertension prevalence have been observed in the United States. A recent report from the CARDIA study, however, documents impressive regional differences in changes of blood pressure in a cohort at each of four sites followed periodically over 7 years.¹ Compared with Chicago, Minneapolis, and Oakland, although there were no regional differences at baseline, the highest incidence and prevalence of elevated blood pressure at 7 years was observed in Birmingham. These regional differences in blood pressure and in change of blood pressure over time suggest hypotheses about environmental contributions to elevated blood pressure.

The potential significance of the relatively high blood pressures in Birmingham is highlighted by an increased relative risk of stroke mortality that has persisted in the southeastern United States for more than five decades, despite the overall nationwide decline in stroke mortality.² Although the specific geographic boundaries may be changing somewhat, the southeastern region of the United States has been referred to as the Stroke Belt. Factors that account for the existence of the Stroke Belt have not been clearly defined, and it has been suggested that geographic variation in hypertension prevalence does not account for the large geographic variation of stroke occurrence or stroke mortality.³ However, the percentage of hypertensive individuals with diastolic pressures 115 mm Hg is higher in the Southeast than in any other region of the United States, and increased rates of hypertensive heart disease have also been observed in the Stroke Belt.^{4 5} Results of the CARDIA cohort, followed longitudinally, lend further credence to the hypothesis that elevated blood pressure is an important contributor to increased stroke mortality in the southeastern United States.

The CARDIA data also document marked racial and sex variations in incidence and prevalence of elevated blood pressure. Overall, the prevalence of elevated blood pressure is greater in blacks than in whites and greater in men than in women. In addition, at the 7-year follow-up, the variable rates of elevated blood pressure among black men in the different CARDIA study sites is particularly striking. The highest prevalence and incidence of elevated blood pressure was observed in black men residing in Birmingham.

The black-white blood pressure differences in CARDIA are consistent with results of a larger survey in the United States, the Third National Health and Nutrition Examination Survey (NHANES). In that survey, the age-adjusted prevalences of hypertension in non-Hispanic blacks and whites were 32.4% and 22.6%, respectively.⁶ Between NHANES I (1971-1974) and NHANES III (1988-1991), the age-adjusted prevalence of hypertension declined in every age-sex-race subgroup except for black men 50 years old.⁷ Furthermore, in blacks, hypertension appears earlier than in whites, is generally more severe, and results in higher rates of morbidity and mortality from stroke, heart failure, left ventricular hypertrophy, and end-stage renal disease.⁸ In the Stroke Belt, stroke mortality rates are highest for black men.²

Both environmental factors and genetic factors may contribute to these regional and racial variations of blood pressure. Furthermore, the same environmental factors may contribute to both geographic and racial blood pressure differences. Regional and international comparisons suggest that blood pressure levels, the increase of blood pressure with age, and the prevalence of hypertension vary among societies. Studies of societies undergoing "acculturation" and studies of migrants from a less to a more urbanized setting indicate a profound environmental contribution to blood pressure.⁹ Although the known environmental exposures leading to hypertension are difficult to quantify, it has been estimated that these exposures collectively account for up to 25% of the variance in blood pressure within societies.¹⁰ Environmental factors to consider include nutrient intake and level of physical activity, exposure to environmental toxins (eg, lead and cadmium), psychological stress, and possibly climate.

Cross-sectional studies document an association between body weight (or body mass index) and blood pressure, and in longitudinal studies, there is a direct correlation between change in weight and change in blood pressure over time.¹¹ It has been estimated that 60% of hypertensives are >20% overweight. In the CARDIA study, however, there were no significant geographic differences of body mass index at the 7-year follow-up that would account for the geographic variations of elevated blood pressure. Data for weight gain over time are not presented for each of the four study sites. Physical activity scores were consistently lower in Birmingham than in the other three sites, and conceivably this may contribute to the higher incidence of elevated blood pressure in Birmingham.

A high NaCl intake convincingly contributes to elevated arterial pressure in a number of genetic and acquired models of experimental hypertension.¹¹ The chimpanzee is phylogenetically close to the human, and in a carefully controlled study, it was recently demonstrated that addition of NaCl to the usual diet of the chimpanzee over 20 months results in a significant elevation of blood pressure.¹² This increase was completely reversed within 6 months of cessation of the high NaCl intake. In the human, evidence for an association between NaCl intake and blood pressure is provided by both observational and interventional studies. Although the overall impact of dietary NaCl on blood pressure within a population is modest, it has been estimated that the reductions of blood pressure observed in intervention trials of sodium restriction would reduce risks of stroke by 15% and coronary heart disease by 6%. Overall blood pressure responses to salt restriction within a population may mask individual variability. Greater responsiveness has been observed in older individuals; in individuals with higher blood pressures; and in controlled trials, with increasing duration of salt restriction. Furthermore, a familial resemblance of the change of blood pressure in response to salt restriction has been described, and a high NaCl intake in infancy may contribute to higher blood pressures in adolescence.¹³

Blood pressure responses to NaCl may also be modified by other components of the diet.¹¹ Dietary intakes of potassium or calcium below the recommended daily allowances potentiate NaCl-induced increases of blood pressure, and conversely, high dietary intakes of potassium or calcium attenuate NaCl-induced hypertension in several animal models. In societies with high potassium intakes, both mean blood pressure and the prevalence of hypertension tend to be lower than in societies with low potassium intakes, and among individuals within a population, there is an inverse correlation between potassium intake and blood pressure. This inverse association is more prominent on a high-NaCl diet, and the urine sodium/potassium ratio is a stronger correlate of blood pressure than either sodium or potassium alone. Obesity and relatively high sodium and low potassium intakes have also been associated with hypertension prevalence among populations of West African origin in West Africa, the Caribbean, and the United States.¹⁴

Similar to potassium, within and among populations there is an inverse association between dietary calcium intake and blood pressure, and low calcium intakes are associated with higher levels of blood pressure and with an increased prevalence of hypertension.¹¹ Similarly, there is suggestive evidence for an association between lower amounts of magnesium in the diet and higher levels of blood pressure. Furthermore, persons consuming vegetarian diets tend to have lower blood pressures than nonvegetarians. Vegetarian diets are usually high in potassium, magnesium, fiber, and carbohydrate content and low in saturated fats.

In the CARDIA study, nutrient intake was assessed on the basis of a 1-month dietary history. Estimated sodium intakes were higher and potassium and magnesium intakes were lower in Birmingham than in the other three sites. Overall, black men had the highest sodium intakes and the lowest potassium and magnesium intakes of all race-sex groups, and this pattern of nutrient intake was most marked among black men in Birmingham. Calcium intakes were not reported. The authors conclude that geographic variations in elevated blood pressure persisted after adjustment for dietary intake. However, although estimates of electrolyte intake based on diet history may detect differences between groups, they are not sufficiently accurate or reliable to document an individual's absolute sodium consumption.¹⁵ Consequently, on the basis of the data presented, it is reasonable to hypothesize that higher sodium and lower potassium and magnesium intakes contribute to the regional and racial variations of blood pressure observed in CARDIA.

Blood pressure may also be affected by intakes of other nutrients.¹¹ There is a J-shaped relationship between alcohol consumption and blood pressure. Light drinkers have lower blood pressures than teetotalers, whereas compared with nondrinkers, individuals consuming three or more drinks per day show a small but significant elevation of blood pressure. In CARDIA, geographic differences in incidence of elevated blood pressure are reportedly not explained by differences in alcohol intake. Limited evidence suggests a direct association between diets high in saturated fats and blood pressure, and many populations with low mean blood pressure levels consume diets low in total fat and saturated fatty acids. Conversely, diets high in -3 saturated fatty acid content may be associated with lower blood pressures. Several recent observational studies suggest that blood pressure level is also inversely associated with dietary protein consumption. No data are presented in CARDIA comparing consumption of these nutrients by geographic region, and theoretically, geographic differences of unmeasured nutrients (as well as exposure to environmental toxins such as lead and cadmium) could contribute to geographic differences of blood pressure.

Psychosocial stress is another environmental factor that may be associated with higher levels of blood pressure and with an increased prevalence of hypertension in different geographic regions and in blacks. In contrast to most black communities in the United States, average blood pressure and prevalence of hypertension are lower in black communities in Africa in which a more traditional way of life is maintained.¹⁴ In the United States, among black adolescents and adults, an inverse relationship between socioeconomic status and blood pressure has been repeatedly demonstrated, with socioeconomic status measured as education, occupation, and/or area of residence.¹⁶ The CARDIA data do not permit comparison of stress in the four study sites. Low environmental temperature is another stressor that is inconsistently associated with higher levels of blood pressure¹⁷ ; however, in the CARDIA study, it is unlikely that lower temperatures account for the higher blood pressure levels observed in Birmingham.

On the basis of population and twin and adoption studies, it has been estimated that 35% of blood pressure variance is heritable, 15% is attributable to the environment, and the remaining 50% is determined by the impact of environment on the individual.¹⁰ Blood pressure variability within populations is greater in those populations with higher levels of blood pressure, suggesting that individuals vary in their responsiveness to environmental stressors.¹⁸ For example, family studies and twin studies suggest a heritable contribution to salt sensitivity of blood pressure.¹¹ Blacks excrete sodium less efficiently than whites, and it has been estimated that >50% of black hypertensives in the United States are salt sensitive. In both blacks and whites, there is evidence for heritability of sodium excretion and levels of hormones that regulate sodium excretion.¹⁹ Family studies and twin studies suggest that the blood pressure responses to mental stress and physical stresses are also heritable, and normotensive individuals with a positive family history of hypertension have augmented blood pressure responses to standardized stressors.²⁰ In CARDIA, the striking geographic variation of incidence of elevated blood pressure among black men also raises the possibility of varying genetic sensitivities to environmental stressors.

Despite evidence for heritability, essential hypertension is a complex trait that does not exhibit classic mendelian modes of inheritance attributable to a single gene locus. Currently, except for rare monogenic hypertensive diseases, no major genes have been identified as primary determinants of hypertension. In view of the genetic heterogeneity of the US population, it is unlikely that genetic factors account for the regional variation of blood pressure observed in CARDIA. However, it is likely that a genetic predisposition influences the phenotypic variation of blood pressure in any individual in response to an environmental stressor. Until the genetic determinants of hypertension have been identified, it will be difficult to convincingly separate out the genetic and environmental contributions to geographic variation of blood pressure. It is probable that a relatively large number of mutations will be found, each of which by itself may have a small impact on blood pressure level.

At present, results of the CARDIA study indicate that geographic region is a risk factor for the development of elevated blood pressure. The study also reaffirms the importance of nutrient intake as one contributor to geographic variation of blood pressure.

	Footnotes

 
The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.

	References

Top Introduction References

 

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