Published Research Showing a Possible Link Between Environmental Mercury Exposure and Heart

Toxic Effects of Mercury on the Cardiovascular System

Contents:

(Then abstracts follow below).

1. Marked elevation of myocardial trace elements in idiopathic dilated cardiomyopathy compared with secondary cardiac dysfunction. Frustaci et al., (1999). J. Am. Coll. Cardiol. 33:1578-83. (10334427)
2. Intake of Mercury From Fish, Lipid Peroxidation, and the Risk of Myocardial Infarction and Coronary, Cardiovascular, and Any Death in Eastern Finnish Men. Jukka et al., (1995) Circulation. 91:645-655. (91/3/645)
3. Effects of mercury on the isolated heart muscle are prevented by DTT and cysteine. Vassallo et al., (1999). Toxicol. Appl. Pharmacol. 156:113-118. (10198276)
4. The chamber exposure of laboratory rats to metal oxides originating from metal producing industry. Kovacikova and Chorvatovicova (1997). Physiol. Res. 46:41-45. (9728520)
5. Mercury effects on the contractile activity of isolated heart muscle. Oliveira et al., (1994). Toxicol. Appl. Pharmacol.128:86-91. (8079358)
6. Mercury compounds: lipophilicity and toxic effects on isolated myocardial tissue. Halbach (1990). Arch. Toxicol. 64:315-319. (2386431)
7. The relationship between mercury from dental amalgam and the cardiovascular disease. Siblerud (1990). Sci. Total Environ.99:23-35. (2270468)
8. Hemodynamic and electrophysiological effects of mercury in intact anesthetized rabbits and in isolated perfused hearts. Rhee and Choi (1989). Exp. Mol. Pathol.50:281-290. (2721650)
9. Cardiovascular homeostasis in rats chronically exposed to mercuric chloride. Carmignani and Boscolo (1984). Arch. Toxicol. Suppl. 7:383-388. (6596006)
10. Mechanisms in cardiovascular regulation following chronic exposure of male rats to inorganic mercury. Carmignani et al., (1983). Toxicol. Appl. Pharmacol.69:442-450. (6879611)
11. Mortality in mice infected with an amyocarditic coxsackievirus and given a subacute dose of mercuric chloride.South PK et al., (2001). TJ. Toxicol Environ Health A. 63(7):511-23. (11497332)

Citations Chosen by:Boyd Haley, Ph.D., Chairman of Chemistry Department, University of Kentucky, USA

Abstracts:

1. Published Research Showing A Possible Link Between Environmental Mercury Exposure and Heart Disease

Marked Elevation of Myocardial Trace Elements in Idiopathic Dilated Cardiomyopathy Compared With Secondary Dysfunction

1Frustaci, A., 2Magnavita, N., 1Chimenti, C., 2Caldarulo, M., 3Sabbioni, E., 3Pietra, R., 4Cellini, C., 4Possati, G.F. and 1Maseri, A.

1Department of Cardiology, 2Department of Occupational Medicine, and 3Department of Cardiac Surgery, Catholic University, Rome Italy and CEC 4Environmental Institute Joint Research Center Ispra, Rome, Italy

Journal of the AmericanCollege of Cardiology

Vol. 33, No. 6, 1999, pp. 1578-1583

Objectives: We sought to investigate the possible pathogenic role of myocardial trace elements (TE) in patients with various forms of cardiac failure.

Background: Both myocardial TE accumulation and deficiency have been associated with the development of heart failure indistinguishable from an idiopathic dilated cardiomyopathy.

Methods: Myocardial and muscular content of 32 TE has been assessed in biopsy samples of 13 patients (pts) with clinical, hemodynamic and histologic diagnosis of idiopathic dilated cardiomyopathy (IDCM), all without past or current exposure to TE. One muscular and one left ventricular (LV) endomyocardial specimen from each patient, drawn with metal contamination-free technique, were analyzed by neutron activation analysis and compared with 1) similar surgical samples from patients with valvular (12 pts) and ischemic (13 pts) heart disease comparable for age and degree of LV dysfunction; 2) papillary and skeletal muscle surgical biopsies from 10 pts with mitral stenosis and normal LV function, and 3) LV endomyocardial biopsies from four normal subjects.

Results: A large increase (>10,000 times for mercury and antimony) of TE concentration has been observed in myocardial but not in muscular samples in all pts with IDCM. Patients with secondary cardiac dysfunction had mild increase (<5 times) of myocardial TE and normal muscular TE. In particular, in pts with IDCM mean mercury concentration was 22,000 times (178,400 ng/g vs. 8 ng/g), antimony 12,000 times (19,260 ng/g vs. 1.5 ng/g), gold 11 times (26 ng/g vs. 2.3 ng/g), chromium 13 times (2,300 ng/g vs. 177 ng/g) and cobalt 4 times (86.5 ng/g vs. 20 ng/g) higher than in control subjects.

Conclusions: A large, significant increase of myocardial TE is present in IDCM but not in secondary cardiac dysfunction. The increased concentration of TE in pts with IDCM may adversely affect mitochondrial activity and myocardial metabolism and worsen cellular function.

To order a copy of this abstract or a complete copy of this study from the National Library of Medicine see the following:

Marked elevation of myocardial trace elements in idiopathic dilated cardiomyopathy compared with secondary cardiac dysfunction. Frustaci et al., (1999). J. Am. Coll. Cardiol. 33:1578-83. (10334427)

2. Intake of Mercury From Fish, Lipid Peroxidation, and the Risk of Myocardial Infarction and Coronary, Cardiovascular, and Any Death in Eastern Finnish Men. Jukka et al., (1995) Circulation. 91:645-655. (91/3/645)

Intake of Mercury From Fish, Lipid Peroxidation, and the Risk of Myocardial Infarction and Coronary, Cardiovascular, and Any Death in Eastern Finnish Men

Jukka T. Salonen, MD, PhD, MScPH; Kari Seppänen, MSc; Kristiina Nyyssönen, MSc; Heikki Korpela, MD, PhD; Jussi Kauhanen, MD, PhD; Marjatta Kantola, MSc; Jaakko Tuomilehto, MD, PhD; Hermann Esterbauer, PhD; Franz Tatzber, PhD; Riitta Salonen, MD, PhD

From the Research Institute of Public Health (J.T.S., K.S., K.N., J.K., R.S.) and Departments of Community Health and General Practice (H.K.) and Chemistry (M.K.), University of Kuopio, Finland; the Department of Epidemiology and Health Promotion (J.T.), the National Public Health Institute of Finland, Helsinki, Finland; and the Institute of Biochemistry (H.E., F.T.), University of Graz, Austria.

Correspondence to Prof Jukka T. Salonen, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland.

Background Even though previous studies have suggested an association between high fish intake and reduced coronary heart disease (CHD) mortality, men in Eastern Finland, who have a high fish intake, have an exceptionally high CHD mortality. We hypothesized that this paradox could be in part explained by high mercury content in fish.

Methods and Results We studied the relation of the dietary intake of fish and mercury, as well as hair content and urinary excretion of mercury, to the risk of acute myocardial infarction (AMI) and death from CHD, cardiovascular disease (CVD), and any cause in 1833 men aged 42 to 60 years who were free of clinical CHD, stroke, claudication, and cancer. Of these, 73 experienced an AMI in 2 to 7 years. Of the 78 deceased men, 18 died of CHD and 24 died of CVD. Men who had consumed local nonfatty fish species had elevated hair mercury contents. In Cox models with the major cardiovascular risk factors as covariates, dietary intakes of fish and mercury were associated with significantly increased risk of AMI and death from CHD, CVD, and any death. Men in the highest tertile (2.0 µg/g) of hair mercury content had a 2.0-fold (95% confidence interval, 1.2 to 3.1; P=.005) age- and CHD-adjusted risk of AMI and a 2.9-fold (95% CI, 1.2 to 6.6; P=.014) adjusted risk of cardiovascular death compared with those with a lower hair mercury content. In a nested case-control subsample, the 24-hour urinary mercury excretion had a significant (P=.042) independent association with the risk of AMI. Both the hair and urinary mercury associated significantly with titers of immune complexes containing oxidized LDL.

Conclusions These data suggest that a high intake of mercury from nonfatty freshwater fish and the consequent accumulation of mercury in the body are associated with an excess risk of AMI as well as death from CHD, CVD, and any cause in Eastern Finnish men and this increased risk may be due to the promotion of lipid peroxidation by mercury.

Mercury Ups Heart Disease Risk

Science Daily Magazine

Co-authors include Jyrki K.Virtanen M.S.c., R.D.; Sari Voutilainen Ph.D., R.D.; Tiina H. Rissanen, M.Sc, R.D.; Jaakko Mursu, M.Sc, R.D.; Meri Vanharanta, M.Sc, R.D.; Kari Seppanen; and Jari Laukkanen, M.D.

American Heart Association Meeting Report 04/24/2002

HONOLULU, April 24 - Finnish men with the highest concentrations of mercury in their hair also had the highest death rates from cardiovascular disease, congestive heart failure and stroke, according to a study presented today at the American Heart Association's Asia Pacific Scientific Forum.

Mercury content in the hair is a marker for the amount of methyl mercury, a toxic form of the element, accumulated in the body by eating contaminated fish. Some scientists believe that the amalgam in dental fillings may also be a significant source of mercury, but questions remain about whether the mercury in dental fillings, which is inorganic, is absorbed into the body.

"Although consumption of fish may be healthy in general, some fish may contain methyl mercury in amounts harmful for humans," says study author Jukka T. Salonen, M.D., Ph.D, MScP.H., professor of epidemiology at the Research Institute of Public Health at the University of Kuopio in Finland.

In the Kuopio Ischemic Heart Disease Risk Factor (KIHD) study, a total of 2,005 men without heart disease, between 42 and 60 years old were divided into four groups based on the mercury content of their hair, and tracked for an average of 12 years.

Heart disease was defined as a history of an acute coronary event, like a heart attack, or angina pectoris, stroke or other cardiovascular event. The researchers controlled for other risk factors that could have affected their results, including age, levels of high-density lipoprotein (HDL, "good" cholesterol), low-density lipoprotein (LDL, "bad" cholesterol), triglycerides, family history of coronary heart disease, systolic blood pressure, weight and intake of fatty acids and antioxidants.

The men who scored in the top 25 percent for hair mercury content had a 60 percent increased risk of death from CVD compared to the men in the lower mercury content. Those same men had a 70 percent increased risk of coronary heart disease alone, says Salonen. The amount of mercury in the hair was determined by flow injection analysis-cold vapor atomic absorption spectrometry and amalgamation, one of several tests available to determine mercury content.

"Men who consumed 30 grams or more of fish daily - had 56 percent higher average hair mercury than those whose daily consumption was less than 30 grams. Those same men also tended to consume certain types of 'predatory' fish," says Salonen. Fish higher in the food chain - i.e., those who eat smaller contaminated fish - tend to have the highest levels of methyl mercury.

"The results also showed that men whose hair mercury levels were in the top 20 percent had a 32 percent faster increase in the thickness of the inner walls of their arteries, a measure of atherosclerosis, compared to men in the rest of the group. Atherosclerosis is the build-up of fatty plaque in arteries and is the underlying process that causes cardiovascular disease.

Previous studies have shown that increasing dietary levels of fish containing omega-3 fatty acids benefits people with cardiovascular disease, as well as healthy people.

The American Heart Association currently recommends that individuals consume two servings of fish weekly, both for the benefits of omega-3 fatty acids, and because fish tends to be low in saturated fats, which contribute to elevated cholesterol levels.

"These results from Kuopio are intriguing, but preliminary, and should be viewed in the context of many other studies that have shown a clear cardiovascular benefit to consuming fish on a regular basis," says Barbara V. Howard, Ph.D., chair of the American Heart Association's Nutrition Committee and president of MedStar Research Institute in Washington, D.C.

"It is important to note that this is an observational study, and the conclusions do not prove a direct relationship between the amount of mercury in the hair and heart attacks. There may be factors such as the socio-economic status of the men or other dietary factors that are hard to measure, that account for the higher risk," says Howard.

Researchers became interested in looking at an association between mercury and cardiovascular disease because mercury has been shown to promote the oxidation of low-density lipoproteins in the arteries. Oxidation is a major component in the development of atherosclerosis. In addition, mercury can interfere with the antioxidant effects of selenium, an essential trace element found mainly in plant foods, and in the U.S., in grains and meat.

The KIHD study is an ongoing, population-based study designed to investigate risk factors for cardiovascular diseases and their outcomes among men in Eastern Finland. Previous studies with shorter follow-up periods from the same research group found a strong association between high hair mercury content and an increased risk of death. Researchers wanted to retest these results over a longer follow-up period.

"It should be noted that we are not against eating fish per se," adds Salonen. "What these results mainly say is that one should avoid regular consumption of old, large predatory fish, in which mercury levels are high, especially when caught from sources that are known to have a high mercury content. Our best advice is to consume a variety of fish, preferably young and small, from different lakes and seas in order to avoid possible high local levels of mercury."

The American Heart Association suggests consuming fish such as mackerel, lake trout, herring, sardines, albacore tuna and salmon twice a week.

American Heart Association

3. Effects of mercury on the isolated heart muscle are prevented by DTT and cysteine. Vassallo et al., (1999). Toxicol. Appl. Pharmacol. 156:113-118. (10198276)

Toxicol Appl Pharmacol. 1999 Apr 15;156(2):113-8.

Effects of mercury on the isolated heart muscle are prevented by DTT and cysteine.

Vassallo DV, Moreira CM, Oliveira EM, Bertollo DM, Veloso TC.

Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.

The protective effects of dithiothreitol (DTT, 50 microM) and cysteine (CYS, 100 microM) against toxic effects of HgCl2 (1, 2.5, 5, and 10 microM) were studied in isolated, isometrically contracting rat papillary muscles. Force reduction promoted by Hg2+ was prevented by both DTT and CYS. Also, after both treatments, no significant changes in dF/dt were observed. A progressive reduction in the time to peak tension was observed when increased concentrations of HgCl2 were used after CYS and DTT treatment. This was an indication that the enhancement of calcium release from the sarcoplasmic reticulum produced by mercury was not affected by DTT and CYS. Tetanic contractions were also studied. After treatment with DTT or CYS tetanic tension did not change. No significant reduction of tetanic tension was observed during treatment with 1 microM Hg2+ but its reduction was observed after 5 microM Hg2+. Myosin ATPase activity was also affect by Hg2+, being completely blocked by 1 microM Hg2+ and reduced by 50% with 0.15 microM Hg2+. Full activity was restored by using 500 nM DTT. These findings suggest that several but not all toxic effects of Hg2+ on the mechanical activity of the heart muscle are prevented by protectors of SH groups such as DTT and CYS. The enhancement of the Ca2+ release from the sarcoplasmic reticulum by Hg2+ during activation was not affected by prior treatment with DTT and CYS, suggesting that interactions with SH groups may not be important for the activation of the Ca2+ channel of the sarcoplasmic reticulum. Copyright 1999 Academic Press.

4. The chamber exposure of laboratory rats to metal oxides originating from metal producing industry. Kovacikova and Chorvatovicova (1997). Physiol. Res. 46:41-45. (9728520)

Physiol Res. 1997;46(1):41-5.

The chamber exposure of laboratory rats to metal oxides originating from metal producing industry.

Kováciková Z, Chorvatovicová D.

Institute of Preventive and Clinical Medicine, SlovakAcademy of Sciences, Bratislava, SlovakRepublic.

Laboratory rats were exposed to the inhalation of dust from an agglomeration unit which is the greatest contributor to dust pollution in the vicinity of a mercury producing plant. The exposure lasted for 6 months (4 hours daily, 5 days per week), the concentration of aerosol in the chamber was 10 mg x m(-3). After finishing the exposure, the animals were examined and compared with the controls which were held under standard laboratory conditions. The number of alveolar macrophages was highly elevated (P< 0.001) in the exposed animals, Mg2+ ATPase activity in the heart muscle was decreased. The alanine aminotransferase activity in the serum was not changed, the aspartate aminotransferase was slightly enhanced. No differences in the frequency of abnormal sperm and in the frequency of polychromatic erythrocytes in bone marrow were detected.

5. Mercury effects on the contractile activity of isolated heart muscle. Oliveira et al., (1994). Toxicol. Appl. Pharmacol.128:86-91. (8079358)

Toxicol Appl Pharmacol. 1994 Sep;128(1):86-91.

Mercury effects on the contractile activity of isolated heart muscle.

Oliveira EM, Vassallo DV, Sarkis JJ, Mill JG.

Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.

The toxic effects of HgCl2 (1, 2.5, 5, and 10 microM) were studied in isolated, isometrically contracting rat papillary muscles and frog ventricular strips. In rat papillary muscles 1 microM Hg2+ produced a small increase in the force of contraction. Higher concentrations of HgCl2 produced a dose-dependent decrease in contractile force. The rate of force development was affected differently, increasing at 1 and 2.5 microM Hg2+ and decreasing to control levels at 5 and 10 microM Hg2+. This was the result of a progressive reduction in the time to peak tension observed when HgCl2 concentrations increased. This effect probably reflects the binding of Hg2+ to SH groups inducing Ca2+ release from the sarcoplasmic reticulum. The relative potentiation of postrest contractions was used as an index of sarcoplasmic reticulum activity. It was measured after pauses of increasing duration and was reduced at concentrations of 1 microM Hg2+ when compared to that of the control. A further decrement in the relative potentiation was observed with higher Hg2+ concentrations, indicating that the activity of the sarcoplasmic reticulum was depressed by mercury in a dose-dependent manner. Tetanic contractions were also studied in the rat myocardium. The tetanic tension did not change during treatment with 1 microM Hg2+ but decreased with 5 microM Hg2+, suggesting a toxic effect on the contractile proteins only at high Hg2+ concentrations. Frog ventricular strips were studied using the same HgCl2 concentrations and no effects on either force or relative potentiation were observed. These findings suggest that Hg2+ promotes dose-dependent toxic effects on heart muscle via actions on the sarcolemma, the sarcoplasmic reticulum, and contractile proteins.