Environmental Cadmium Exposure,Hypertension and Cardiovascular Risk

Perry HM Schroeder HA St Louis : Concentration of trace metals in urine of treated and untreated hypertensive patients compared with normal subjects J Lab Clin Med 1955, 46:936. Thispaper was the first report to show a relationship between cadmium and hypertension.

Schroeder HA Vinton WH Jr : Hypertension induced in rats by small doses of cadmium Am J Physiol 1962, 202:515–518. Inthis paper hypertension was induced in rats by chronic exposure to low doses of cadmium, The following papers [3–5] also reported similar results in rats fed low doses of cadmium.

Perry HM Jr Erlanger MW : Metal induced hypertension following chronic feeding of low dose of cadmium and mercury J Lab Clin Med 1974, 83:541–547.

Perry HM Erlanger M Perry EF : Increase in systolic pressure of rats chronically fed cadmium Environ Health Perspect 1976, 28:251–260.

Petring HG Murhty L Sorenson JRJ Levin L Stmmer KL : Effect of sex on oral cadmium dose response in rats: Blood pressure and pharmacodynamics Environ Res 1979, 20:289–299.

Schroeder HA Krokk SS Little JW Livingston PO Myers MAG : Hypertension in rats from injection of cadmium Arch Environ Health 1966, 13:786–789. Hypertensionwas found in rats after acute exposure to cadmium by intravenous injection. Similar results were reported in the following papers [7,8].

Perry HM Jr Yunice A : Acute pressor effects of intra-arterial cadmium and mercury ions in anesthetized rats Proc Soc Exp Bio Med 1965, 120:805–808.

Perry HM Erlanger M Yunice E Schoepfle E Perry EF : Hypertension and tissue metal levels following intravenous cadmium, mercury, and zinc. Am J Physiol 219:755–761.

Perry HM Margaret W Erlanger M : Elevated circulating renin activity in rats following doses of cadmium known to induce hypertension J Lab Clin Med 1973, 82:399–405. Increasedrenin activity was reported as one of the possible mechanisms of hypertension induced by cadmium in rats.

Carnignani M Boscolo P : Cardiovascular responsiveness to physiological agonists of male rats made hypertensive by long-term exposure to cadmium Sci Total Environ 1984, 34:19–33. Inthis report, chronic exposure to cadmium affected several neurohumoral mechanisms that regulate cardiovascular function in rats.

Williams BJ Laubach DJ Nechay BR Steinslan OS : The effects of cadmium on adrenergic neurotransmission in vitro Life Sci 1978, 23:1929–1934. Thisin vitro study using rabbit arteries suggested that the enhancement by cadmium of the arterial response to nerve stimulation might be the mechanism of cadmium-induced hypertension.

Revis N : A possible mechanism for cadmium-induced hypertension in rats Life Sci 1977, 22:479–488. Thisin vitro study using rats suggested that effects of cadmium on noradrenaline metabolism may be a mechanism of cadmium-induced hypertension.

Dalham T Friberg L : The effect of cadmium on blood pressure and respiration and the use of dimercaprol (BAL) as antidote Acta Pharmacol Toxicol 1954, 10:199–203. Inthis report, decrease of blood pressure caused by intravenous injection of cadmium was reported in rabbits. This result was in contrast to that in rats reported by Perry et al. [7,8].

Nishijo M : The effects of cadmium on blood pressure and renal sympathetic nerve discharges in rabbits Jpn J Hyg 1987, 42:874–880. Thisreport also detected a depressor effect of intravenous exposure to cadmium in rabbits.

Thind GS Stephan KT Blakemore WS : Inhibition of vasopressor responses by cadmium. Am J Physiol, 1970, 219:577–583. Thisin vitro study reported the inhibitory effects of cadmium on contractile response of isolated arteries of rabbits. This result is also contrary to hypertension induced by cadmium. The following papers [16–19] are also in vitro studies in rabbits or dogs with the same results.

Toda N : Influence of cadmium ions on contractile response of isolated aortas to stimulatory agents Am J Physiol 1973, 225:350–355.

Hayashi S Toda N : Inhibition by cadmium, verapamil and papaverine of Ca-induced contractions in isolated cerebral and peripheral arteries of the dog Br J Pharmacol 1977, 60:35–43.

Nasu T : Spasmolitic effect of cadmium and cadmium uptake in aorta Br J Pharmacol 1983, 79:751–754.

Nishijo M : The effects of long-term exposure to environmental level of cadmium on arterial strips in rabbits. Jpn J Hyg 42:933–938.

Boscolo P Carmignani M : Mechanisms of cardiovascular regulation in male rabbits chronically exposed to cadmium. Br J Ind Med 1986, 43:605–610. Thoughthe aortic vascular resistance was increased, myocardial contractility was reduced to preserve hemodynamic equilibrium.

Giles W Hume JR Shibata EF : Presynaptic and postsynaptic actions of cadmium in cardiac muscle Fed Proc 1983, 42:2994–2997. Calciuminflux through cell membrane of cardiac single cells of the bull frog is inhibited by cadmium and heart contraction, the increase of which causes hypertension, was also inhibited by cadmium.

Kopp SJ Glonek T Perry HM Jr Erlanger M Perry EF : Cardiovascular actions of cadmium at environmental exposure levels Science 1982, 217:837–838. Thisshows biphasic effects of cadmium on blood pressure dependent on the dose of cadmium, explaining the conflicting results in previous studies.

Kopp SJ Hawley PL : Factors influencing cadmium toxicity in A-V conduction system of isolated perfused rat heart Toxicol Appl Pharmacol 1976, 37:531–544. Thisin vitro study showed that arteriovenous blockage could be induced by cadmium in rats.

Schroeder HA : Renal cadmium and essential hypertension JAMA 1964, 187:358–359. Thispaper showed high cadmium concentrations in renal tissue in hypertensive autopsy cases and proposed that cadmium induce hypertension in man.

Schroeder HA : Cadmium as a factor in hypertension J Chron Dis 1965, 18:647–656. Areview of the studies reporting a relationship between renal cadmium concentration and incidence of hypertension, and the high renal concentration of cadmium or increase in the ratio of cadmium to zinc in autopsy cases dying of hypertensive diseases.

Glauser DG Bello CT Glauser EM : Blood-cadmium levels in normotensive and untreated hypertensive humans Lancet 1976, i:717–718. Increasedblood cadmium concentrations were reported in hypertensive men compared with normotensive controls, although only a small number of subjects were examined.

Medeiros DM Pellum LK : Elevation of cadmium, lead, and zinc in the hair of adult black female hypertensives Bull Environ Contam Toxicol 1984, 32:525–532. Increasedcadmium concentrations in hair were reported in hypertensive black women.

Revis NW Zinsmeister AR : The relationship of blood cadmium level to hypertension and plasma norepinephrine level: A Romanian study. Proc Soc Exp Biol Med 1981:254–260. Incases selected on the basis of smoking status and hypertension, blood cadmium level related to smoking and hypertension after adjustment for differences in age and level of plasma norepinephrine level.

Geiger H Bahner U Anderes S Schaefer RM Schaller KH : Cadmium and renal hypertension J Hum Hypertens 1989, 3:23–27. Thisis a recent report of high urinary cadmium concentrations in patients with hypertension suffering from renal disease suggesting that cadmium may be involved in the development of hypertension in renal disease patients.

Morgan JM : Tissue cadmium concentration in man Arch Intern Med 1969, 123:405–408. Nodifference in tissue concentrations of cadmium was reported in four groups of autopsy cases divided on the bases of antecedent, hypertensive and cardiovascular disease, ischemic cardiac or cerebrovascular disease, neoplastic disease and controls.

Beevers DG Campbell BC Goldberg A Moore MR Hawthorne YM : Blood-cadmium in hypertensives and normotensives Lancet 1976, ii:1222–1224. Nodifference in blood cadmium concentrations in hypertensive patients was detected compared with that in controls matched for age and sex.

Ostrgaard K : Cadmium and hypertension Lancet 1977, i:677–678.

In necropsy cases, renal cadmium concentrations were higher in normotensives than in hypertensives. This is the opposite relationship to that reported by Schroeder et al. [1,24,25].

Cummins PE Dutton J Evans CJ Wynford D Morgan D Sivyer A : An in-vivo study of renal cadmium and hypertension Euro J Clin Invest 1980, 10:459–461. Renalcadmium levels of hypertensive patients undergoing treatment were measured in vivo using the technique of partial-body neutron activation analysis and no difference from cadmium concentrations of normotensives was found.

Kato T Abe K : Toyama prefecture In Cadmium Studies in Japan. A Review. Edited by Tsuchiya K. Tokyo: Kodansha, 1978: 224–225. Thisis a review of the epidemiological and clinical features of itai-itai disease patients and residents in the largest cadmium-polluted area in Japan.

Nogawa K : Itai-itai disease and follow-up studies In Cadmium in the Environment. II. Health Effects. Edited by Mariagu JO. New York: John Wiley; 1981:1–37. Anexcellent review of studies of clinical features and follow-up studies of itai-itai disease.

Nogawa K Kawano S : A survey of the blood pressure of women suspected of ‘itai-itai’ disease [in Japanese, with English abstract] Jzen Med J 1969, 3:357–363. Epidemiologicalsurvey of blood pressure in heavily cadmium-exposed women suspected of having bone damage due to itai-itai disease. Their blood pressure was lower than that of inhabitants living in control areas.

Shinoda A Yuri T Nakagawa S : Clinical findings of itai-itai disease patients [in Japanese] Kankyo Hoken Rep 1977, 41:44–52. Astudy of urinary sodium excretion and renin activity of itai-itai disease patients whose blood pressure is lower than that of controls.

Kagamimori S Naruse Y Fujita T Watanabe M Nishino H Shinmura T : Factors associated with blood pressure in females with heavy exposure to cadmium. Bull Environ Contam Toxic 35:386–392. Afollow-up study of blood pressure in women suspected of having itai-itai disease reported decreased blood pressure for 10 years.

Kasuya M Nishijo M Teranishi H Kubota Y Kato T Aoshima K : The relationship between blood pressure level and other health indices among inhabitants living in cadmium-polluted Jinzu River basin [in Japanese]. Kankyo Hoken Rep 1987 53:237–239. Inthis paper, blood pressure levels of itai-itai disease patients and their families were reported to be lower than those of controls and related to the degree of renal tubular dysfunction.

Aoshima K Kasuya M : Environmental exposure to cadmium and effects on human health. Part 3. The results of blood examinations and blood pressure in inhabitants of the cadmium-polluted Jinzu River basin in Toyama Prefecture [in Japanese, with English abstract] Jpn J Hyg 1983, 43:949–955. Amonginhabitants of a cadmium-polluted Toyama area, the authors demonstrated a negative correlation between blood pressure and urinary sodium excretion which is increased by renal dysfunction induced by cadmium.

Japan Public Health Association Cadmium Research Committee: Studies of health effects of cadmium [in Japanese] Kankyo Hoken Rep 1989, 53:69–345. Thisreport includes a comparison of prevalence of hypertension between inhabitants of seven cadmium-polluted areas and control areas.

Staessen J Bulpitt CJ Roels H Bernard A Fagard R Joossens JV : Urinary cadmium and lead concentrations and their relation to blood pressure in a population with low exposure Br J Ind Med 1984, 41:241–248. Theauthors recognized a negative relationship between blood pressure and urinary β₂-microglobulin concentration among inhabitants with low cadmium exposure in Belgium.

Staessen J Amery A Bernard A Bruaux P Buchet JP Bulpitt CJ : Blood pressure, the prevalence of cardiovascular diseases, and exposure to cadmium: A population study Am J Epidemiol 1991, 134:257–267. Thisis a population study designed to clarify the hypothesis that cadmium exposure induces an increase in blood pressure or prevalence of hypertension among inhabitants living in heavy and low cadmium-polluted areas in Belgium.

Engvall J Perk J : Prevalence of hypertension among cadmium-exposed workers. Arch Environ Health 40:185–190. Theauthors reported that the period of employment was longer for hypertensive male workers of an alkaline battery factory than for normotensive workers.

Roels HA Lauwerys RR Buchet JP Lijnen P Houte GV : Urinary kallikrein activity in workers exposed to cadmium, lead, or mercury vapour Br J Ind Med 1990, 47:331–337. Thelevel of urinary kallikrein activity was reduced in cadmium-exposed workers. Though the subjects were normotensive, the authors suggested that blood pressure regulation might be affected by cadmium.

Shigematsu I Takeuchi J Minowa M Nagai M Usui T Fukushima M : A retrospective mortality study on cadmium-exposed pollution in Japan [in Japanese] Kankyo Hoke Rep 1980, 46 (part 2):1–71. Thisis the first and largest population study of the mortality of inhabitants in a Japanese polluted area. The mortality rates from all causes or specific causes were calculated in polluted areas in Akita, Toyama and Nagasaki Prefectures. Mortality rates from hypertensive diseases or heart diseases were decreased.

Nishijo M Nakagawa H Morikawa Y Tabata M Senma M Miura K : Mortality of inhabitants in a cadmium polluted area: 15-year-follow-up Occu Environ Med 1995, 52:181–184. Themortality from cardiovascular diseases of retinol-binding protein-positive inhabitants living in a cadmium-polluted area in Ishikawa Prefecture was higher than that of retinol-binding protein-negative subjects, but no cause of the increase in heart failure was indicated.

Nakagawa H Nishijo M Morikawa Y Tabata M Senma M Miura K Urinary b2-microglobulin concentration and causes of death of inhabitants living in a cadmium-polluted area [in Japanese]. Kankyo Hoken Rep 1993, 60:142–145. Thisis also a follow-up study of cadmium polluted inhabitants in Ishikawa Prefecture that reported that the mortality rate from ischemic heart disease of β₂-microglobulin positive men was decreased, though the mortality rate from heart failure was high.

Armstrong B Kazantzis G : The mortality of cadmium workers Lancet 1983, i:1425–1427. Thisis a follow-up study of cadmium-exposed workers in the UK that proposed the possibility of excess deaths from respiratory diseases. No increase in mortality rate from hypertensive disease was recognized.

Inskip H Beral V McDowell M : Mortality of Shipham residents: 40-years-follow-up Lancet 1982, i:896–899. Asmall excess of death from hypertensive disease and cerebrovascular diseases was recognized in this follow-up study of residents of Shipham, UK, a village with high soil cadmium levels.

Bierenbaum ML Fleischman AI Dunn J Arnold J : Possible toxic water factor in coronary heart-disease Lancet 1975, i:1008–1009. Astudy designed to investigate the relationship between risk factors of coronary heart disease and hardness of water caused by high concentrations of metals including cadmium.

Carroll RE : The relationship of cadmium in the air to cardiovascular disease death rates. 1966, JAMA 198:267–269. Astatistical analysis of mortality from cardiovascular diseases and cadmium concentration in the air.

Hickey RJ Schoff EP Clelland RC : Relationship between air pollution and certain disease death rates Arch Environ Health 1967, 15:728–738. Thisis also a statistical analysis of mortality and concentrations of heavy metals in the air of some populations in cities in the USA.

Manthey J Stoeppler M Morgenstern W Nussel E Opherk D Weintraut A : Magnesium and trace metals: Risk factors for coronary heart disease? Associations between blood levels and angiographic findings Circulation 1981, 64:722–729. Inpatients who visited the hospital for evaluation of chest pain, blood concentration of cadmium was correlated with cigarette smoking, but no relationship was found between blood cadmium levels and coronary lesions assessed by coronary angiography.

Kagamimori S Watanabe M Nakagawa H Kawano S Okumura Y Kawano S : Case control study on cardiovascular function in females with a history of heavy exposure to cadmium Bull Environ Contam Toxicol 1986, 36:484–490. Thisreport suggests that cadmium could affect the electrocardiogram of itai-itai disease patients, characterized by decreased frequency of ischemic change and prolongation of PR-interval.

Thun MJ Osorio AM Schober S Hannon WH Lewis B Halperin W : Nephropathy in cadmium workers: Assessment of risk from airborne occupational exposure to cadmium Br J Ind Med 1989, 46:689–697. Systolicblood pressure of factory workers exposed to airborne cadmium in the USA was associated with cadmium dose in multivariate analysis.

Tsorahan Waterhouse JAH : Mortality study of nickel-cadmium battery workers by the method of regression models in life tables Br J Ind Med 1983, 40:293–300. Themortality rate from diseases of the circulatory system of male factory workers exposed to cadmium in the UK was significantly lower than that of the general population of England and Wales, but no association between mortality and exposure of cadmium was found by the regression models in life tables.

Elinder CG Kjellstrom T Hogstedt C Andersson K Spang G : Cancer mortality of cadmium workers Br J Ind Med 1985, 42:651–655. Themortality rate from cardiovascular diseases of factory workers in Sweden was not significantly different from that of the general Swedish population.