Effects of elements in human blood pressure control

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<ul><li><p>Effects of Elements in Human Blood Pressure Control</p><p>HUBERT F. LOYKESt. Vincent Charity Hospital, Department of Medicine, </p><p>Cleveland, OH 44115</p><p>Received March 1, 2001; Revised July 17, 2001; Accepted September 17, 2001</p><p>ABSTRACT</p><p>This review enumerates and discusses the elements involved in the con-trol of human blood pressure via a historical evolutionary form. The olderand most recent element literature presentations were researched usingMEDLINE and a manual review of documents cited. Independent dataextraction and cross-referencing was performed. Of the 28 known elementsthat can influence blood pressure, 15 were found to be involved in humanblood pressure regulation. The elements were divided into four groups: elec-trolyte, composed of sodium, potassium, calcium, and magnesium; metal,which included zinc, copper, and iron; toxic, made up of lead, mercury, cad-mium, barium, thallium, arsenic; miscellaneous (lithium and selenium). Evo-lutionary historical data, possible mechanisms of actions, and interactionsbetween elements that have been shown to influence blood pressure are dis-cussed. Controversy exists over the therapeutic use of elements to alter bloodpressure but is absent in the case of the toxic group where preventive controlis a proven public health matter. The significance of these 15 elements in theregulation of human blood pressure has been established and ongoing stud-ies will continue to reinforce their influence and importance.</p><p>Index Entries: Blood pressure; elements; hypertension; minerals.</p><p>INTRODUCTION</p><p>High blood pressure is the most common disease in industrializedsociety and the ubiquitous elements play an important role in the patho-physiology and control of blood pressure. Of the 28 known elements (1),only 15 can be classified as important participants in human blood pres-sure control. The major participating elements identified as having animportant role in blood pressure regulation are sodium, calcium, potas-</p><p>Biological Trace Element Research 193 Vol. 85, 2002</p><p> Copyright 2002 by Humana Press Inc.All rights of any nature, whatsoever, reserved.0163-4984/02/85030193 $14.25</p></li><li><p>sium, and magnesium. Elements that play a minor role are identified asthe five trace elements copper, zinc, selenium, lithium, and iron and the sixtoxic ones: lead, cadmium, arsenic, barium, mercury, and thallium. Thisarticle provides an overview from an early historical perspective of theevolutionary concepts to our presentday knowledge of the relationship ofelements to human blood pressure regulation.</p><p>MATERIALS AND METHODS</p><p>The initial older and most recent presentations of element literaturewere researched using independent data extraction and cross-referencing.Manual medical review and computerized MEDLINE equipment wereemployed using the following terms: elements and blood pressure, trace ele-ments and blood pressure, and hypertension and minerals. The criteria forinclusion were assembled in a historical and chronological order of the ini-tial article on the subject. Subsequent references of new information,including epidemiological studies and meta-analysis when available, werefollowed by mechanisms of action and interactions between elements andended with the most recent new data on the subject.</p><p>ELECTROLYTE GROUP</p><p>Sodium</p><p>The relationship of the electrolytes to the elements sodium, potas-sium, calcium, and magnesium (Table 1) are highly relevant to the patho-physiology of blood pressure regulation. It was suggested as early as 1904that sodium in a high-salt intake may be implicated in the development ofhigh blood pressure (2). This idea did not gain support until Kempner (3),in the 1940s, reported that subjects with severe hypertension loweredblood pressure when treated with rigid salt restriction (e.g., rice diet).Since these reports, several studies have described societies in which rou-tine higher intakes of sodium increased blood pressure (4). Conversely, itwas shown that in societies with low-sodium intake, there is little or noincrease in blood pressure with age (5). Urinary sodium and blood pres-sure findings in the standardized INTERSALT study of 52 centers (32countries) showed a significant positive association in 8 centers and a neg-ative association in 2 centers (6). The purpose of that study was to providedefinitive data of the effect of sodium on blood pressure; however, 5 yrafter publication, the debate continued. Subsequently, it was concludedthat the general relationship between blood pressure control and saltingestion has not been sufficiently documented. A recent meta-analysis byGroudal et al. (7) of 58 trials of hypertensive persons did not support ageneral recommendation to reduce sodium intake; however a small reduc-</p><p>194 Loyke</p><p>Biological Trace Element Research Vol. 85, 2002</p></li><li><p>tion in dietary salt in older individuals will cause a fall in blood pressure(8). One effect of the mechanism of sodium restriction shows a rise inplasma norepinephrine that results in increasing the release of renal nor-epinephrine (9). In light of the relatively weak relationship betweendietary sodium and blood pressure, Messerli et al. (10) hypothesized in1997 that a strong correlation exists between salt intake and hypertensiontarget organ disease (heart, kidney, brain, and vasculature). This inde-pendent correlation between salt intake and target organ disease suggeststhat dietary sodium is a direct perpetrator of cardiovascular disease, par-ticularly in salt-sensitive patients.</p><p>Sodiums role in salt-sensitive subjects (Table 2) is widely acceptedand there is general agreement that the mechanism of salt sensitivity isrelated to the following: (1) plasma renin levels (11); (2) alterations in cal-cium metabolism (12); (3) some aspects of sympathetic nervous systemfunction (813); (4) the severity of the hypertension (14). Other informationpertinent to complications of hypertension is seen in patients withsodium-sensitive essential hypertension, where blood pressure fails to fallduring the night and this nocturnal hypertension may be a marker forgreater risk (15). Information regarding an association between the differ-ent levels of sodium intake in relation to morbidity and mortality has beenlacking. However, Alderman et al. (16) presented evidence that supportsthe likelihood that lowering sodium through dietary intervention will leadto a decrease risk of stroke and myocardial infarction, presumably by areduction in blood pressure. Also, Elliot et al. (17) concluded that a strongpositive association of urinary sodium in relation to the systolic pressureof individuals concurs with cross-population findings and supports rec-</p><p>Elements in Hypertension 195</p><p>Biological Trace Element Research Vol. 85, 2002</p><p>Table 1Elements Effects on Blood Pressure</p><p>* Increased and decreased blood pressure effects.</p></li><li><p>ommendations for reduced high-salt intake for the prevention and controlof adverse blood pressure levels. Insulin resistance has been demonstratedin patients with essential hypertension, and insulin-moderated sodiumretention is believed to contribute to hypertension in these individuals(18). In the latest collaborative study (19), it was concluded that over-weight adults having a high normal blood pressure, weight loss andreduction in sodium intake, individually and in combination, were foundto be effective, especially in lowering both systolic and diastolic bloodpressure in the short term. Thus, sodium is an important element in thecontrol of human blood pressure. Despite conflicting data regarding saltand hypertension, it is clear that at least in the elderly and salt-sensitivesubjects, salt may increase blood pressure.</p><p>Potassium</p><p>The old name potash was given to the element potassium and aninadequate amount of dietary potassium may be associated with essentialhypertension. As early as 1902, Bunge (20) pointed out that the electrolytepotassium (Table 2) antagonizes the biological effects of sodium and Thomp-son and McQuerrie (21) in 1934 reported that potassium salts could lowerblood pressure in hypertensive subjects. The first epidemiological study (22)was performed in 1959 in two Japanese communities with similar saltintakes. In the village where the blood pressure was lower, the potassium</p><p>196 Loyke</p><p>Biological Trace Element Research Vol. 85, 2002</p><p>Table 2Elements and Systems in Blood Pressure Control</p><p>Systems that may be involved relative to elements in the control of human blood pressure.References pertaining to the source of the information is provided in parentheses</p></li><li><p>intake was much higher. The role of potassium, however controversial, stemsfrom experimental studies in several models of hypertension (23). A contem-porary epidemiologic study demonstrated a greater prevalence of hyperten-sion among population groups ingesting diets low in potassium (24). Watsonet al. (25), studying blacks and whites living in the same geographic area,found a higher incidence of hypertension and lower potassium intake whereurinary sodium potassium ratio was 4.1 for the blacks and 2.9 for the whites.A meta-analysis of 33 randomized controlled trials (26) support the premisethat low potassium intake may be an important factor in the genesis of highblood pressure and that potassium supplementation may be especially use-ful for black patients as well as those who have difficulty lowering dietaryintake of sodium. In contrast, the Hypertension Preventive CollaborativeResearch Group (27) found little evidence of the potassium-supplementationlowering effect of blood pressure in normotensive persons. The most recentdata strongly suggest that potassium supplementation is particularly impor-tant in patients being salt sensitive ingesting more salt than other patients(28). Tobian et al. (29) demonstrated that high potassium diets confer protec-tion against brain hemorrhage in spontaneously hypertensive rats with orwithout blood pressure reduction and Khaw and Barrett-Connor (30)described an inverse relationship between potassium intake and stroke riskin a study of American white men and women and concluded that potassiumdepletion augments human stroke-associated mortality. The mechanism ofpotassiums effect on blood pressure is not clear. Possible actions are throughnaturetic and diuretic effects, central and peripheral effects upon the nervoussystem, and alterations in the reninangiotensin aldosterone axis (31). Potas-sium plays an important role in the control of blood pressure, especiallyregarding diet and stroke prevention.</p><p>Calcium</p><p>The mineral ion calcium has a relationship to blood pressure home-ostasis. The case for the electrolyte calcium effect on blood pressure (Table 2)was made, later than that of the other cations in 1955, when Schroeder andPerry (32) demonstrated the antihypertensive effect of chelating agents inassociation with ion-binding calcium. Subsequently, in the 1960s, clinicaland experimental reports appeared noting the relationship between hyper-parathyroidism and hypertension (33). Interest in the effect of calcium onblood pressure levels was stimulated by the observation that persons drink-ing hard water, having a high concentration of calcium, had a low mor-tality and low incidence of cardiovascular disease (34). A great deal ofconfusion exists over the effects of both dietary and serum calcium levels onhypertension. To help clarify this, Harlan et al. (35), in the early 1970s ana-lyzed the data collected by the National Center for Health Statistics Healthand Nutrition Examination Survey I (Hanes I). Among their findings, thegroup noted that calcium was the nutrient for which reduced intake wasmost consistent in people with systolic hypertension. Conversely, hypercal-</p><p>Elements in Hypertension 197</p><p>Biological Trace Element Research Vol. 85, 2002</p></li><li><p>cemia has been shown to be hypertensive in acute studies as well as inchronic azotemic patients (36). Augmenting the picture, calciums blood-pressure-lowering effects (Table 1) have been reported in both men andwomen as well as in the elderly (37). Epidemiological studies (38) by Beli-zoon and Villar, using meta-analysis, described finding an inverse relation-ship to exist between calcium intake and gestational hypertension ineclampsia. Subsequently, Bucher et al. (39) found that supplementation dur-ing pregnancy leads to an important reduction in systolic and diastolicblood pressure in the preeclampsia patient. Comparing black and white nor-motensive men, Lyle et al. (40) concluded that calcium supplements pro-duced a modest but significant decrease in blood pressure in both races. Onepossible mechanism of calcium supplements may be the production of reninin patients with low renin activity (Table 2) and low serum-ionized calciumlevels, blood pressure is lowered (41). In the latest reports, Weinberger et al.(42) concluded that calcium supplements decreased blood pressure inpatients identified, a priori, as being salt sensitive, although not in the gen-eral population. In a longitudinal study (37) of young children, the mainfinding was that calcium intake was inversely related to systolic blood pres-sure. Furthermore Dwyer et al. (43) found that with a low intake of calciumin the diet, African-American adolescents lowered their diastolic blood pres-sure with calcium supplements. Finally, Griffith et al. (44) concluded thatcalcium derived from a natural good source may have as much as twice thebeneficial effect of calcium supplements. This element has important appli-cations to the control of blood pressure in general medicine and obstetrics.</p><p>Magnesium</p><p>Magnesium is a trace mineral acting primarily as an intracellular ion.Over the past decade, clinical, epidemiological, and experimental data sug-gest that magnesium, the fourth most abundant cation in the human body,plays an important role in blood pressure control. Interest in the element isrelatively new in the treatment of hypertension; however, a report by Black-fan and Hamilton (45) in 1925 found that an infusion of magnesium salt low-ered blood pressure (Table 1) in some patients with hypertension. Lazard(46) in the same year reported giving an obstetrical patient intervenous mag-nesium sulfate in treating eclampsia. Likewise, McCall and Sass (46) demon-strated that, in toxemia of pregnancy, treatment with magnesium sulfatedecreased blood pressure. In 1957, the effect of magnesium action accordingto Elkington (46) was that the element caused peripheral vasodilitation witha subsequent fall in blood pressure. Aside from obstetrics, parenteral mag-nesium sulfate has been used in the treatment of severe hypertension ofglomerular nephritis (47). Epidemiological studies have described an inverserelationship between dietary intake of magnesium and blood pressure (48).Magnesium levels are not necessarily indicative of total-body magnesium;consequently, the ability to determine a deficiency is problematic. Altura andAltura (49) stated that magnesium, particularly in conjunction with other</p><p>198 Loyke</p><p>Biological Trace Element Research Vol. 85, 2002</p></li><li><p>nutrients, does contri...</p></li></ul>