Q J Med 1999; 92: 601-607
© 1999 Association of Physicians
Commentary papers |
Salt, obesity, and alcohol fail to induce a lasting rise of blood pressure with age, and may be independent of renocortical vasculopathy
From the Department of Pathology, Louisiana State University Medical Center, New Orleans, USA
Professor R.E. Tracy, Department of Pathology, Louisiana State University Medical Center, 1901 Perdido Street, New Orleans LA 70112, USA. e-mail: rtracy{at}lsumc.edu
Summary
Essential hypertension has a multitude of aetiologies, environmental circumstances that impact harmfully upon blood pressure levels. These aetiologies fall into two types: a reversible type that requires continuous exposure to the inciting agent to sustain the elevated blood pressure, and a persistent type which introduces some form of permanent change, presumably in body tissues. Available data on salt overload, obesity, and alcohol tend to cast these agents as reversible, without persistent effects. Agents of the reversible type emerge here as unlikely candidates for explaining the rise of blood pressure with age. Evidence reviewed here implicates intimal fibroplasia in renocortical arteries as the accumulated record that causes rising of blood pressure with age by Goldblatt mechanisms actuated through nephron heterogeneity. Such mechanisms could explain the persistent effects that propel the rise of blood pressure with age at varying rates among world-wide populations. These findings offer a new starting place for efforts to discover the aetiological agents that propel the rise of blood pressure with age, agents that apparently do not include salt, obesity, or alcohol.
Introduction
Essential hypertension has a multitude of aetiologies, environmental circumstances that impact harmfully upon blood pressure levels. These sources of noxious influence fall broadly into two types, reversible and persistent. Agents of the reversible type elevate blood pressure as long as they are present, but allow total relief of the effect upon withdrawal; this category probably includes salt loading, alcohol, and obesity. Agents of the persistent type act to impel a progressive rise of blood pressure with age. They presumably do this by inducing hypothetical tissue changes of uncertain character that in some way sustain high blood pressure. The agents in the persistent category are entirely unknown. They apparently do not include salt loading, alcohol, or obesity, as demonstrated in the data to be reviewed here.
Blood pressure rises with age. For this to occur, some kind of record must be kept in the tissues that registers the passage of time. Antihypertensive medications can uncouple the tissue record from its influence on blood pressure, thereby lowering blood pressure. But in the vast majority of patients, the effect of medication regresses in full upon withdrawal of treatment.1 The tissue record is persistent, and cannot be erased by any known means.
This paper explores the possibility that ageing changes in the renal microvasculature might be the permanent record that underlies the rise of blood pressure with age.
Sodium loading
Detailed documentation strongly supports the placement of dietary sodium loading into the category of reversible aetiologies for hypertension.2,3 In the Intersalt study, 24-h urinary excretion of sodium was used to estimate habitual daily salt intake among members of 52 communities around the world.2 The average effect of increasing salt use by 100 mmol/24h was to elevate blood pressure by 4.5/2.3 mmHg systolic/diastolic between populations. Between individuals, within populations, the estimates of the effect ranged from 3.1 to 6.0 mmHg systolic and 0.1 to 2.5 mmHg diastolic pressure.
In the Intersalt study, the effect of salt loading increased with age and blood pressure. By age 55 years, a loading of 100 mmol/24 h raised systolic pressure by 10–11 mmHg and diastolic by 6 mmHg. These are almost precisely the same magnitudes of reduction that are expected from withdrawal of dietary salt. Analysis of 78 trials of salt restriction concluded,3 `A reduction of sodium intake of 100 mmol/24 h ... would lower systolic pressure by an average of 10 mmHg in those with high blood pressure. For diastolic pressure ... about half these values.'
These two bodies of data converge upon a clear conclusion: Those Intersalt populations with high salt intake experience lifelong elevations of blood pressure, and that experience may leave no lasting alterations of the blood pressure. Withdrawal of salt is expected to remove the effect fully, even after 35 years of sustained impact upon the body tissues. This line of inference suggests that salt loading does not influence the tissue record that underlies rising blood pressure.
Alcohol
Available data seem to support the placement of alcohol into the category of reversible agents for high blood pressure.4,5 A review of multiple reports concluded,4 `In general, persons who drink heavily appear to have systolic blood pressures 5 to 10 mmHg higher and diastolic blood pressures 3 to 6 mmHg higher than persons who on an average drink very little.' The effect was often found to be J-shaped, with the elevations of blood pressure confined to the heaviest drinkers.
The lowering of blood pressure by withdrawal of alcohol was assessed in a randomized crossover trial.5 The investigators concluded, '... a predominant effect on systolic blood pressure with a fall of 1.1 mmHg for every 100-ml reduction in ethanol intake ...' Hence, a reduction of alcohol intake by 450–910 ml per week, equivalent to 2.1–4.3 drinks per day, should fully cancel the average elevation of systolic pressure of 5 to 10 mmHg seen in the heaviest drinkers.4
These studies are indecisive, and not entirely comparable with each other. At face value, however, the conclusion resembles that for salt: heavy drinkers experience elevated blood pressure over a period of years which evidently leaves no permanent residue in the tissues. The effect is strictly functional, and requires continuous exposure to the inciting agent to sustain the elevated blood pressure.
Obesity
Some evidence suggests that obesity should be placed into the category of reversible agents.6-9 A summation of findings from three NHANES reports concluded,6 `The difference in diastolic blood pressure is about 7 mmHg between the highest and lowest quintile of BMI category in men. The mean systolic blood pressure is about 8 mmHg higher for men between the highest and lowest quintile of BMI categories.' The mean BMI (body mass index) was 20.8 in the lowest and 33.8 in the highest quintile, equivalent to a difference of 41.2 kg. This difference corresponds to the difference of 8 mmHg in systolic pressure, or 1.9 mmHg per 10 kg of body weight in men of 70 inches height. Similar calculations for women of 66 inches height yield 2.7 mmHg per 10 kg of body weight.
Few studies have successfully quantified the effect on blood pressure from weight reduction by dietary means. One study concluded,7 `... the mean 6-month weight loss was 5.7 kg and the 6-month BP decreases were almost identical in the 2 trials (3.8/2.5 mmHg and 3.7/2.7 mmHg, respectively).' These data yield 3.8/0.57=6.7 mmHg systolic blood pressure reduction per 10 kg body weight loss. Two other studies offer data for calculating comparable estimates,8,9 yielding, respectively, 2.5 and 6.0 mmHg reduction in systolic blood pressure per 10 kg weight loss.
These data sets are not strictly comparable to each other for a variety of reasons. The findings nevertheless fit provisionally with the view of obesity as a reversible type of aetiological agent. Overweight subjects experienced many years of elevated blood pressure attributable to obesity, yet withdrawal of the obesity appears to produce a prompt fall in blood pressure, as if the effects of those many years had never transpired.
High blood pressure may not drive the rise of blood pressure with age
Data given in a recent report from the Intersalt study10 persuasively support a surprising conclusion: high blood pressure itself may not accelerate the rise of blood pressure with age. That report provides, for each of 52 communities, regression equations relating systolic blood pressure to age over the range of ages 20–60 years. Figure 1
summarizes those data.
|
The Intersalt data allow calculation of systolic pressure prevailing in each of the 52 communities at age 20 years. Figure 1
plots these levels (horizontal axis) against the subsequent rise to age 60 years (vertical axis). The rise in systolic pressures ranged from <1 to >12 mmHg per decade of ageing, with most populations clustering around 4 mmHg per decade. Average systolic pressure at age 20 years ranged from 96 to 118 mmHg, with most populations clustering around 110 mmHg.
The initial level of systolic pressure at age 20 years had no discernible influence upon the subsequent rise in systolic pressure (Figure 1). Some of the populations began adult life with prevailing levels for systolic pressure around 115 mmHg. These populations on average exhibited the same rate of subsequent rise as the populations beginning around 100 mmHg. The surprising conclusion is hard to escape: High blood pressure left no evidence of tissue changes that might later support high blood pressure.
Nephron heterogeneity
The rise of blood pressure with age calls for an explanation. One such explanation, as elaborated by Goldblatt,11 emphasizes the vasculopathies of the microscopic renal arteries and arterioles.
The interlobular arteries of the ageing kidney progressively accumulate a fibroplastic change.12-15 This is an incremental replacement of withering media with an expanding fibroplastic intima (Figure 2). It is easy to envision that these fibroplastic changes gradually introduce ever worsening strictures upon the interlobular arteries. The effect of this hypothetical process would be to generate nephron heterogeneity.
|
16%od. od=200 µm; PAS-stained paraffin section.The theory of nephron heterogeneity proposes that some (ischaemic) nephrons deprived of adequate blood flow send out renin, thereby raising blood pressure. Other (hyperaemic) nephrons raise blood pressure by retaining salt and water in response to the prevailing renin levels from the ischaemic sources. Seally et al.16 explain how this uniquely disturbed setting, nephron heterogeneity, can sustain both high and low renin forms of hypertension. Data reviewed elsewhere17 generally tend to support the conclusion that nephron heterogeneity exists in essential hypertension, even when usual function tests yield results within normal limits.
Similar patterns in the rise with age of blood pressure and renovasculopathy
Blood pressure rises with age faster in some populations than others (Figure 3, right chart). A similar pattern emerges when fibroplastic intimal thickness is measured in the interlobular arteries of renal samples obtained at autopsy in those populations (Figure 3, left chart). Details of those graphs and their derivations are given elsewhere.14 The autopsy cases used here omit all cases of cardiovascular death or other condition known to correlate with hypertension; these omissions generate a basal group that produces an autopsy series approximately representative of each sampled population.18 These data tend to support the theory of nephron heterogeneity, and to suggest that measurements of vasculopathy might permit calculation of blood pressure in each of the age groups.
|
Relationship of renovasculopathy to blood pressure
Figure 4 offers a way to visualize how blood pressure might relate to pathological intimal thickenings of interlobular arteries. The thickening, Rc, on the horizontal axis, is determined as in Figure 2. Blood pressure on the vertical axis was obtained from hospital out-patient records averaged over the last few years of observation. These averages were converted into mean blood pressure (MBP) to neutralize the effect of widening pulse pressure consequent to stiffening of the aorta as it ages, MBP=(S+2D)/3. Details of these data are given elsewhere.14
|
The grey zone labelled `Type 1' represents the region of Figure 4
that contains `hypertensive' subjects with mild or minimal fibroplastic renovasculopathy, Rc. The zone labelled `Type 2' represents `hypertensive' subjects with severe degrees of vas culopathy. These newly introduced terms are defined as Type 1: vertical departure upward from the regression line, and Type 2: diagonal departure along the regression line. Subjects in the upper part of the Type 2 grey zone have both Type 1 and Type 2 hypertension coexisting. Estimating blood pressure from renovasculopathy for groups of subjects
In Figure 4, the measured Rc on the horizontal axis corresponds to a position on the diagonal line, which in turn corresponds to a level of MBP on the vertical. Hence, Rc is transformed into MBP by tracing this course on the graph, like reading a nomogram. In practice, the MBP is calculated from Rc through a polynomial regression equation.13 This calculation captures only the Type 2 component of hypertension. The omission of the Type 1 component makes the result highly inaccurate for each individual. However, in the average of a group, the individual inaccuracies cancel each other, leaving the mean value on or near the diagonal line. The Maltese crosses, representing the age group means, illustrate this principle in Figure 4.
The coupling of renovasculopathy to the rise of blood pressure with age
Figure 5 reiterates the data in Figure 3, and also introduces similar data for women. MBP calculated from Rc is plotted against MBP derived from community survey data. The diagonal line reproduces the regression line from Figure 4, (with units of measure of Rc transformed into mmHg) to allow comparison of that line with the data from the various populations.
|
The group averages tend to cluster along the diagonal in Figure 5
. This is the pattern expected when Type 2 hypertension varies between groups. The variations in Type 1 hypertension (vertical departures) between individuals, as seen in Figure 4, cancel each other within groups, leaving no substantial Type 1 effects between groups. A technical detail of Figure 5 perhaps calls for comment. Data points depart perceptibly from the dashed line near its two ends, especially for groups of women. These departures expose flaws in the polynomial equation used for estimating MBP from renovasculopathy. These flaws call for refinement by further studies. The evolution of Type 2 hypertension in ageing subjects
Figure 5 offers a dynamic image of how hypertension progresses: Starting at ages 20–29 years, data points fall near the lower left end of the dashed line. As the men of New Orleans grow older, their data points move upward and rightward along the dashed line, faster for Black than for White men. The men of Bombay follow more slowly, so that by ages 50–59 years they overtake the New Orleans men of ages 30–39 years. In all circumstances, the progression with age is predominantly along the regression line, without important vertical departures from it.
These findings favour the view that blood pressure rises with age entirely, or almost entirely from the progression of Type 2 hypertension. Type 1 effects (vertical departures) make little if any contribution to the process. These findings have far-reaching implications. For instance, salt loading appears to be a Type 1 influence that does not affect the progression of Type 2 hypertension.
Using data reviewed earlier in this report,2,3 a hypothetical subject can be constructed, and placed into the context of Figure 5. Salt loading of this composite subject beginning at age 20 years ought to elevate blood pressure in a sustained vertical departure from the diagonal line (a Type 1 effect). At a later age of 30, 40, or 50 years, the subject should return to the diagonal upon withdrawal of the inciting influence, the salt loading. Those many years of elevated blood pressure had no lasting effect upon the blood pressure level, after withdrawal of the salt. The Type 1 hypertension, induced by salt, had no effect upon the ongoing evolution of the Type 2 process. Similar arguments apply directly to alcohol and obesity, also.
The aetiology of Type 2 hypertension
Recent reports indicate that renofibroplasia appears to progress about 40% faster in New Orleans than in Mexico.19,20 These two populations exemplify the extremes of human potential that have so far arisen in world-wide studies. A recent review19 of available evidence suggests that Mexican Americans have renofibroplasia and blood pressure more like those in the USA than in Mexico. Moreover, recent immigrants to Dallas from Latin America tended to reveal renofibroplasia like that in Mexico, while migrants of long residence tended to resemble native-born USA populations.
These provocative observations suggest that the ageing of the renal microvasculature, and its attendant Type 2 hypertension, may be in part governed by alterable environmental influences. The challenge now is to search for the identity of those influences. The search can be narrowed by de-emphasizing unlikely candidates, such as salt, alcohol, obesity, or indeed, any factors with reversible effects upon the blood pressure, since blood pressure itself is among these unlikely candidates. Efforts might be more fruitfully directed to other aspects of cultural differences across geographic boundaries. Likely candidates should have the property of lacking any direct action upon the blood pressure itself.
References
1.
Schmieder RE, Rockstroh JK, Messerli FH. Antihypertensive therapy. To stop or not to stop? JAMA 1991;265:1566–71.
2.
Elliot P, Stamler J, Nichols R, Dyer AR, Stamler R, Kesteloot H, Marmot M for the Intersalt Cooperative Research Group. Intersalt revisited: further analyses of 24 hour sodium excretion and blood pressure within and across populations. Br Med J 1996;312:1249–53.
3. Law MR, Frost CD, Wald NJ. By how much does salt reduction lower blood pressure? III -Analysis of data from trials of salt reduction. Br Med J 1991;302:819–23.
4. Moore RD, Levine DM, Southard J, Entwisle G, Shapiro S. Alcohol consumption and blood pressure in the Maryland Hypertension Survey. Am J Hypertens 1990;3:1–7.[Web of Science][Medline]
5.
Puddey IB, Beilin LJ, Vandongen R, Rouse, IL, Rogers P. Evidence for a direct effect of alcohol consumption on blood pressure in normotensive men. A randomized controlled trial. Hypertension 1985;7:707–13.
6. Ernst NC, Obarzanek E, Clark MB, Briefel RR, Brown CD, Donato K. Cardiovascular health risks related to overweight. J Am Diet Ass 1997;97(suppl.):S47-51.[Web of Science][Medline]
7.
The Trials of Hypertension Prevention Collaborative Research Group. Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high-normal blood pressure. Arch Int Med 1997;157:657–67.
8.
Whelton PK, Appel LJ, Espeland MA, Applegate WB, Ettinger WH, Kostis JB, Kumanyika S, Lacy CR, Johnson KC, Folmar S, Cutler JA, for the TONE Collaborative Research Group. Sodium reduction and weight loss in the treatment of hypertension in older persons. A randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). JAMA 1998;279:838–46.
9.
Davison MH, Hauptman J, DiGirolamo M, Foreyt JP, Halsted CH, Heber D, Heimburger DC, Lucas CP, Robbins DC, Chung J, Heymsfield SB. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat. JAMA 1999;281:235–42.
10. Intersalt Cooperative Research Group. Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24-hour urinary sodium and potassium excretion. Br Med J 1988;297:319–28.
11.
Goldblatt H. The renal origin of hypertension. Physiol Rev 1947;27:120–65.
12. Bell ET. Renal Diseases. Philadelphia, Lea and Febiger, 1950:329–95.
13. Tracy RE, Lanjewar DN, Ghorpade KG, Valand AG, Raghuwanshi SR. Renovasculopathies in elderly normotensives of Bombay, India. Geriat Nephrol Urol 1997;7:101–9.[Medline]
14.
Tracy RE. Heterogeneity of vascular findings in the kidneys of patients with benign essential hypertension. Nephrol Dial Transpl 1999; 14:1634–9.
15.
Fishberg AM. Anatomic findings in essential hypertension. Arch Int Med 1925;35:650–68.
16. Sealy JE, Blumenfeld JD, Bell GM, Pecker MS, Sommers SC, Laragh JH: On the renal basis for essential hypertension: Nephron heterogeneity with discordant renin secretion and sodium excretion causing a hypertensive vasoconstriction- volume relationship. J Hypertens 1988;6:763–77.[Medline]
17. Tracy, R.E. Nephrosclerosis from childhood to old age; A viewpoint. Geriat Nephrol Urol 1992;1:201–11.
18.
McFarlane MJ, Feinstein AR, Wells CK, Chan CK: The `epidemiologic necropsy'. JAMA 1987;258:331–8.
19. Tracy RE, Guileyardo JM. Renovasculopathies of hypertension in Hispanic residents of Dallas, Texas. Arch Med Res 1999;30:40–8.[Web of Science][Medline]
20. Tracy RE, Rodriguez HAM: Renovasculopathies of hypertension in Mexico City. Arch Path Lab Med 1996; 120:261–6.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. J. McNamara, B. Diouf, M. D. Hughson, R. N. Douglas-Denton, W. E. Hoy, and J. F. Bertram Renal pathology, glomerular number and volume in a West African urban community Nephrol. Dial. Transplant., August 1, 2008; 23(8): 2576 - 2585. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||