A clinical study of dialysis-related osteoarthropathy in long-term hemodialysis patients

Amyloid osteoarthropathy has been seen frequently in long-term hemodialysis (HD) patients, in which the bone X-ray examination reveals characteristic cystic radiolucency (CRL) of the carpal bone, shoulder joint, hip joint and knee joint, and destructive spondylarthropathy (DSA) of cervical vertebrae. To clarify the clinico-pathological significance of CRL and DSA in HD-related amyloidosis, we investigated the grade and frequency of CRL or DSA and these relationship with age, HD duration, primary diseases, osteoarticular symptoms and blood analysis in 817 HD patients (492 male and 325 female, age: 52.6 + 15.5 years, dialysis duration: 6.8 + 5.4 years). The number of cases with osteoarticular symptoms increased with the prolongation of HD duration. CRL and DSA were observed even in patients without osteoarticular symptoms: 26.7% for carpal bone, 26.2% for shoulder joint, 17.3% for hip joint and 22.2% for DSA. The grade and frequency of CRL and DSA also increased in accordance with age and HD duration. In patients with CRL of the carpal bone, shoulder CRL was noticed in 39.7%, hip CRL in 25.8%, and DSA in 14.3% of cases, respectively, and these frequencies increased with the prolongation of HD duration. In the carpal CRL negative group, shoulder CRL was noticed in 14.6%, hip CRL in 7.5%, and DSA in 6.0%, respectively. Although there was no relationship between CRL or DSA and serum beta 2-MG level in any of the cases, the serum beta 2-MG level was lower in patients with HD showing shoulder CRL (+2) and DSA (+) for more than 16 years. No significant relationship was noticed between CRL or DSA and serum C-PTH and aluminum level. These results suggested that aging was related to CRL or DSA formation in dialysis-related amyloidosis. The findings also suggested that systemic bone X-ray examination should be considered in patients with carpal bone CRL, high-age patients and long-term HD patients even without osteoarticular symptoms.     

Neural activity affects distribution of glutamate receptors during neuromuscular junction formation in Drosophila embryos

The prevalence of diseases associated with obesity, such as cardiovascular disease and diabetes mellitus, is higher in the spinal cord injury (SCI) population. Specifically, the mortality rate for cardiovascular disease is 228% higher in the SCI population. In addition, 100% of SCI individuals have osteoporosis in the paralysed extremities. These diseases are related to physical activity level, the level of the spinal cord lesion, and time post injury. Physically active SCI men and women have above-average fat mass (16 to 24% and 24 to 32%, respectively, compared with 15% for able-bodied men and 23% for able-bodied women), while sedentary SCI individuals have 'at-risk' levels of body fat (above 25% and 32%, respectively). The proportions and densities of the 3 main constituents comprising the fat-free body (mineral, protein and water) are altered following SCI. Bone mineral content decreases by 25 to 50%, and the magnitude of reduction is dependent on the level, completeness and duration of SCI. Because of denervation resulting in skeletal muscle atrophy, total body protein reduces by 30%, and total body water relative to bodyweight decreases by 15% following SCI. Indirect methods based on 2-component body composition models assume constant proportions and densities of mineral, protein, and water in the fat-free body. As a result, prediction equations based on 2-component models yield invalid estimates of fat and fat-free mass in the SCI population. Therefore, future research needs to directly quantify the proportions and densities of the constituents of the fat-free body in the SCI population relative to age, sex, physical activity level, level of the spinal cord lesion and time post injury, and to develop equations based on multicomponent body composition models.     

The effect of varying levels of dietary vitamin A on immune response in the chick

The anti-oxidant metabolism was studied at different times after sub-culture in 2 colon cell lines previously characterized for their growth and differentiation properties. The HT29 cell line is mainly composed of proliferative and undifferentiative cells, while the derived 5-fluorouracil (FUra)-adapted cells undergo growth-dependent differentiation, which is complete at post-confluence. In the 2 cell lines, all the anti-oxidant parameters studied appeared to be related to proliferation, with increased activity of superoxide dismutase (SOD) 1 and 2, catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GSR), and glutathione transferase (GST), and decreased glucose-6-phosphate dehydrogenase (G6PD) activity and glutathione content, in parallel with slowing down of proliferation. At post-confluence, these metabolic parameters remained stable, except for GPX activity, which continued to increase, and CAT activity, which decreased. The amounts of SOD1, SOD2 and CAT immunoreactive proteins, estimated by Western blotting, appeared to be correlated to their respective enzymatic activities. SOD1, CAT and GST activity and glutathione content, which remained at similar levels in the 2 cell lines for all times studied, appeared unrelated to the differentiation process. GSR and GPX activity, which was lower in FUra-adapted than in parental cells only at post-confluence, could be considered as markers of differentiated cells. The higher SOD2 and lower G6PD activity observed in FUra-resistant cell in comparison with parental cells at all times after sub-culture could be characteristic both of differentiative and of differentiated cells. Interestingly, cytogenetics have previously indicated that deletions of the long arm of chromosome 6, which carry the gene for SOD2, were frequently observed in parental but not in FUra-adapted cells. These results demonstrate that modifications of the anti-oxidant metabolism occur in relation with proliferation and differentiation, and suggest a particular role for SOD2 in these cellular processes.     

Age-dependent modifications in rat hepatocyte antioxidant defense systems

BACKGROUND/AIMS: Age-dependent changes in the hepatic antioxidant systems were studied in hepatocytes from newly weaned (21 days) to 30-month-old rats. RESULTS: Biphasic changes were observed in superoxide dismutase (SOD), glucose-6-phosphate dehydrogenase (G6PDH) and malic enzyme (ME), in which noticeable decreases were detected in hepatocytes from newly weaned to 6-month-old rats: Cu-Zn SOD decreased to 46% (p < 0.001), Mn SOD to 41% (p < 0.001), G6PDH to 71% and ME to 19% (p < 0,001), and significant increases were observed from 6 to 30 months. In hepatocytes from 6- to 30- month-old rats the enzymes involved in antioxidant defense underwent increases in their activities as well in their mRNA: Cu-Zn SOD (142%, p < 0.001), catalase (182%, p < 0.001) and glutathione peroxidase (325%, p < 0.001). However, chronological decreases were observed in the levels of reduced glutathione (69%, p < 0.001), in the GSH/GSSG ratio (78%) and in protein thiol groups (55%, p < 0.001), with concomitant increases in peroxides (155%, p < 0.001) and malondialdehyde (142%, p < 0.001) levels. DNA ploidy was also assayed by flow cytometry; a sharp increase in tetraploid (2.5-40.1%, p < 0.001) and octoploid (0.1-16.1%; p < 0.001) populations, and a noticeable decrease in diploid hepatocytes (92.9-34.3%; p < 0.001), were observed. Populations involved in 2C-->4C DNA synthesis decreased from 3.6 to 0.9% (p < 0.001), while those involved in 4C-->8C increased from 0.9% to 5.2% (p < 0.001). A hypodiploid population (apoptotic cells) was detected from 12 months, increasing thereafter. CONCLUSIONS: These results show that the antioxidant cell defense system increases with age but the rate of reactive oxygen species generation exceeds the induced antioxidant ability, generating a situation that favors oxidative stress and peroxidation. The progressive polyploidization is accompanied by changes in the proliferative potential that decreases from 2C to 4C and increased from 4C to 8C. The relationship between the modifications of the oxidant/antioxidant system and increased polyploidy is not clear and may be interpreted as two independent manifestations of the aging process.     

The frequency of surgery of benign prostatic hypertrophy

OBJECTIVES: To calculate the incidence of surgical treatment of benign prostatic hyperplasia (BPH) in two French departments, Indre-et-Loire and C her, in order to deduce the incidence in France. METHODS: All patients operated for BPH by transurethral resection or transvesical prostatectomy were counted prospectively over a 6-month period by all surgeons of the Indre-et-Loire and Cher departments. Collection of case files was complete and based on BPH resection specimens sent to pathology. 506 patients were included in this survey. RESULTS: The mean age of the patients was 71.8 years. 78% of patients were operated by a private urologist, and 93% by a specialist urologist. The mean postoperative stay was 7.1 days and varied according to the patient's age, the weight of the prostate and the site of the operation (university hospital, private establishment and general hospital). This study allowed calculation of the annual incidence of surgery for BPH in these 2 departments: 822/100,000 men over the age of 50 years. The maximal incidence was observed during the 7th decade of life: 1,742/100,000. In our study, private urologists operated 76 patients for BPH per year. CONCLUSION: Extrapolation of these results to the French population indicates an annual incidence of surgery for benign prostatic hyperplasia in France of 776/100,000 men over the age of 50 years. On the basis of this incidence, an estimated 55,000 to 65,000 men are operated for BPH per year in France.     

The American Urological Association symptom index for benign prostatic hyperplasia as a function of age, volume and ultrasonic appearance of the prostate

PURPOSE: Our study was conducted to reveal quantitatively the relative effects of age and ultrasonic appearance of benign prostatic hyperplasia (BPH) on urinary symptoms as evaluated by the American Urological Association (AUA) symptom index score. MATERIALS AND METHODS: In 929 examinees (732 with a normal prostate and 197 with BPH) on a mass screening program for prostatic diseases using transrectal ultrasonography in Japan, the AUA symptom score was compared to age, prostatic volume and presumed circle area ratio using simple and multiple regression analyses. RESULTS: Simple regression analysis demonstrated the symptom score to correlate significantly with age (R = 0.162, p < 0.0001), prostatic volume (R = 0.072, p = 0.0281) and presumed circle area ratio (R = 0.150, p < 0.0001). However, multiple regression analysis demonstrated that age and presumed circle area ratio were significant independent determinants of the total symptom score. Among 7 symptoms included in the AUA symptom index weak stream and hesitancy scores were not influenced by age, prostatic volume or presumed circle area ratio. CONCLUSIONS: As a parameter representing the degree of BPH in terms of the severity of urinary symptoms, presumed circle area ratio was preferable to prostatic volume. Regression analyses confirmed again that the AUA symptom index was influenced considerably by age and was not specific to BPH.     

Seasonal changes in the activity of antioxidative defense in the kidneys of the euthermic ground squirrel (Citellus citellus)

The aim of this work was to determine the activity of the antioxidant enzymes: superoxide dismutase (EC 1.15.1.1; SOD), catalase (EC 1.11.1.6; CAT), glutathione peroxidase (EC 1.11.1.9; GSH-Px), glutathione-S-transferase (EC 2.5.1.18; GST), glutathione reductase (EC 1.6.4.2; GR) and the low molecular mass antioxidants: ascorbic acid (ASA) and vitamin E (vit E) in the kidney of ground squirrels during circannual changes. Keeping the ground squirrel at the temperature of thermic neutrality (30 degrees C) provides a stable euthermic state during the whole year and thus any change is due to the circannual rhythm. The highest specific activity of all examined antioxidative defense enzymes in the kidney was found in the spring, when ground squirrels are seasonally the most active. In the summer, lower specific activity of GSH-Px as well as of SOD and CAT were noted and, when expressed per g wet mass, only a decrease in GSH-Px activity was recorded. In the kidney of ground squirrels kept at 30 degrees C, the lowest specific activity of all examined enzymes was found during the winter and, when expressed per g wet mass, only the SOD activity was lower than in the spring and summer. Higher amounts of vitamins C and E were found in the ground squirrel kidneys in the summer. The results obtained in this work demonstrate that circannual regulation of metabolic activity, which is inherent to seasonal hibernators, is also expressed at the level of antioxidative defense in the kidneys.     

Impaired antioxidant defence in guinea pig heart tissues treated with halothane

PURPOSE: To investigate the effects of halothane and halothane plus vitamin E treatment on myocardial free radical metabolism in guinea pigs. METHODS: Four groups of seven animals were studied: control, halothane, halothane plus vitamin E and vitamin E groups. In the halothane group, halothane 1.5% in oxygen was given for 90 min over three days. In the halothane plus vitamin E group, 300 mg.kg-1.day-1 vitamin E im was started three days before the first halothane treatment and continued for three days. Following sacrifice, the hearts were assayed for superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) and malondialdehyde (MDA) level was determined. Electron spin resonance (ESR) analysis and electron microscopy (EM) were also performed. RESULTS: In the halothane group, SOD activities and MDA concentrations were increased compared with control and GSH-Px and CAT activities were decreased. In the halothane plus vitamin E group, there were no differences in enzyme activity compared with halothane alone but the MDA level was decreased. In the vitamin E group, enzyme activities were increased compared with control. Mainly the CF3CHCl radical was identified by ESR analysis in heart tissues exposed to halothane and the concentration of this radical was reduced by vitamin E. Electron microscopy showed cytoplasmic vacuolisation and dilation in sarcoplasmic reticulum in the heart tissues exposed to halothane: both were prevented by vitamin E. CONCLUSION: Although halothane causes impairment in enzymatic antioxidant defence potential, due to lowered GSH-Px and CAT activity, and accelerates peroxidative reactions in the tissues affected, no subcellular damage occurred. Vitamin E may protect tissues against free radical attack by scavenging toxic free radicals formed in heart tissue during halothane anaesthesia.     

Influence of receptor number on the stimulation by salmeterol of gene transcription in CHO-K1 cells transfected with the human beta2-adrenoceptor

We investigated the behavior of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APx), in potato tubers during storage at low temperature. SOD activity increased temporarily within 3 weeks and was higher at 1 degree C than at 20 degrees C. APx activity also increased more at low (1 degree C) than at higher temperatures (5 and 20 degrees C). The contents of ascorbic acid (AsA), which is the substrate of APx, decreased immediately within 3 weeks and then gradually decreased until 15 weeks. The activity of CAT, the other enzyme which can scavenge hydrogen peroxide, decreased once in the first six weeks and thereafter increased to 15 weeks. Thus, the enhancement of the active oxygen-scavenging system that was induced by low temperature in potato tubers could result not only in a decrease of AsA but also in combined increases in APx and CAT activity whose manners were different.     

Insulin resistance syndrome and fibrinolytic activity: the northern Sweden MONICA study

BACKGROUND: Many studies have, in small and highly selected study populations, described how cardiovascular risk factors tend to cluster in subjects with insulin resistance. Recently, interest has focused on possible relationships between this insulin resistance syndrome and fibrinolysis, and the role of triglycerides in this association. The present study addresses these issues in a general population. METHODS: A subsample of participants in the population-based Northern Sweden MONICA (MONItoring of trends and determinants in CArdiovascular diseases) Study, consisting of 353 men and 403 women in the 25-64 year age range, was investigated. Insulin resistance was estimated indirectly from the fasting levels of insulin and glucose. Fibrinolytic activity was measured both as plasminogen activator inhibitor type 1 (PAI-1) activity and tissue plasminogen activator ((t)PA) activity. RESULTS: Insulin resistance was highly correlated with those cardiovascular risk factors that have been associated with the insulin resistance syndrome, and to the measures of fibrinolytic activity. Subjects in the upper tertile of insulin resistance had a PAI-1 activity that was three times higher than that of the lower third men and twice as high in women. There was a strong interaction between insulin resistance and serum triglycerides. Low versus high levels of both variables together were associated with a fivefold difference in PAI-1 activity in men and a threefold difference in women. The (t)PA activity was inversely correlated to both insulin resistance and serum triglycerides. CONCLUSIONS: In a general population, the 'insulin resistance syndrome' is closely associated with low fibrinolytic activity. Serum triglyceride levels interact with insulin resistance to predict fibrinolytic activity.     

Protein oxidative damage in a transgenic mouse model of familial amyotrophic lateral sclerosis

The Gly93-->Ala mutation in the Cu,Zn superoxide dismutase (Cu,Zn-SOD) gene (SOD1) found in some familial amyotrophic lateral sclerosis (FALS) patients has been shown to result in an aberrant increase in hydroxyl radical production by the mutant enzyme that may cause oxidative injury to spinal motor neurons. In the present study, we analyzed the extent of oxidative injury to lumbar and cervical spinal cord proteins in transgenic FALS mice that overexpress the SOD1 mutation [TgN(SOD1-G93A)G1H] in comparison with nontransgenic mice. Total protein oxidation was examined by spectrophotometric measurement of tissue protein carbonyl content by the dinitrophenylhydrazine (DNPH) assay. Four ages were investigated: 30 (pre-motor neuron pathology and clinical disease), 60 (after initiation of pathology, but pre-disease), 100 (approximately 50% loss of motor neurons and function), and 120 (near complete hindlimb paralysis) days. Protein carbonyl content in 30-day-old TgN(SOD1-G93A)G1H mice was twice as high as the level found in age-matched nontransgenic mice. However, at 60 and 100 days of age, the levels were the same. Then, between 100 and 120 days of age, the levels in the TgN(SOD1-G93A)G1H mice increased dramatically (557%) compared with either the nontransgenic mice or transgenic animals that overexpress the wild-type human Cu,Zn-SOD [TgN(SOD1)N29]. The 100-120-day increase in spinal cord protein carbonyl levels was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoretic separation and western blot immunoassay, which enabled the identification of heavily oxidized individual proteins using a monoclonal antibody against DNPH-derivatized proteins. One of the more heavily oxidized protein bands (14 kDa) was identified by immunoprecipitation as largely Cu,Zn-SOD. Western blot comparison of the extent of Cu,Zn-SOD protein carbonylation revealed that the level in spinal cord samples from 120-day-old TgN(SOD1-G93A)G1H mice was significantly higher than that found in age-matched nontransgenic or TgN(SOD1)N29 mice. These results suggest that the increased hydroxyl radical production associated with the G93A SOD1 mutation and/or lipid peroxidation-derived radical species (peroxyl or alkoxyl) causes extensive protein oxidative injury and that the Cu,Zn-SOD itself is a key target, which may compromise its antioxidant function.     

Surgical treatment of children with medically intractable epilepsy--outcome of various surgical procedures

Although endothelium-dependent vasodilation is impaired in human hypertension, the mechanism underlying this abnormality is not yet completely elucidated. It has been suggested that accelerated inactivation of nitric oxide (NO) due to superoxide anion, which is rapidly removed by superoxide dismutase (SOD) in physiological condition, may be related to hypertension. Therefore, SOD deficiency following an increase in superoxide anion production contributes to a rise in arterial blood pressure (BP). We hypothesized that there is defective endogenous SOD in patients with essential hypertension. To examine this assumption we measured the SOD activities of the erythrocytes in 335 healthy Chinese volunteers (age 2-76 years) and 30 hypertensive patients (age 60-75 years). The SOD activities of the healthy volunteers exhibited decreased trend with advancing aging. There was no significant difference in the SOD activities between men and women in each group. There is significant difference in the SOD activities (1814.35 +/- 250.00 vs 1584.06 +/- 126.19 u/Hb.g; P < 0.001) between the two groups (age 20-59 years; mean age 34 years vs age 60-76 years; mean age 67 years). The SOD activities in patients with essential hypertension were 1322.4 +/- 139.5 u/Hb.g and significantly lower than the corresponding healthy controls (P < 0.05). In the hypertensives, the SOD activities against systolic and diastolic arterial pressure seem to be shown the trend of negative correlation but did not reach the statistical significance. We conclude that the SOD activities in the erythrocytes are reduced in subjects with essential hypertension and increasing aging. The present findings, in a limited data, could suggest that the fall in SOD activities following an increased superoxide anion production with subsequently augmented NO inactivation is, at least in part, involved in the pathogenesis of human hypertension, although the evidence is indirect. The decrease in erythrocyte SOD activities may serve as a function of human aging.     

Cohort differences in disability and disease presence

Using the National Health Interview Surveys conducted from 1982 through 1993, this article examines cohort patterns in disability and disease presence for adults born between 1915 and 1959, at ages ranging from 30 to 69 years. In general, disability decreases for cohorts born between 1916 and the early 1940s (for men) or the early 1950s (for women), but begins to increase for cohorts born after those dates. Later-born cohorts have significantly lower levels of some diseases, most importantly cardiovascular diseases, arthritis, and emphysema. However, some diseases and conditions are more prevalent in later-born cohorts: asthma, musculoskeletal disorders, and orthopedic impairments. The results presented here indicate that adults born in the late 1940s and 1950s will be in better cardiovascular health but may be in worse musculoskeletal condition when they enter old age compared with current cohorts of older persons.     

Cholesterolemia and total, cardiovascular and cancer mortality. Study of a cohort of 220,000 people]

The distribution of cholesterolemia and their relationship to total mortality, cardiovascular mortality, and cancer mortality were studied in a population of 125,513 men and 96,301 women, aged 16-90. Cholesterolemia in the population increases with age, up to age 50-60 for men and 60-70 for women. Beyond these ages, cholesterolemia decreases very significantly for men and moderately for women. Upon global examination of the entire population, the relationship between cholesterolemia and total mortality is observed as a U-shaped curve. The relationship with cancer mortality is slightly negative in men and appears as a U-shaped curve in women. The relationship with cardiovascular mortality in men is strongly positively correlated when adjusted for body mass index, blood pressure, tobacco consumption, gamma GT, and age. This relationship is not significant in women. There is a significant interaction in the relationship between cholesterolemia and mortality in men for weight, body mass index, vital capacity, maximum expiration volume per second, tobacco consumption, urea, serum albumin, hematocrit, hemoglobin, alkaline phosphatases, gamma GT, red cell volume, and sedimentation rate. Age is a fundamental variable to take into account. Thus, in men under 50 years of age at the time of inclusion, the relationship between cholesterolemia and total mortality shows a positive tendency, and the relationship with cardiovascular mortality is strongly positive. In men over 65 years of age, these relationships are negative. The same tendencies exist for cancer mortality. The reasons for these negative relationships may be related to the decreased cholesterol levels in subjects with malnutrition or diseases (essentially hepatic diseases); this is especially true in older subjects. These data push for additional in-depth analysis of these relationships and interactions, according to age categories and detailed causes of mortality. They also reinforce the idea that, in some patients, low cholesterolemia appears to be a marker for predisposition or the result, but not a cause, of cancer.     

Effect of Lanthanum on Rice Growth and Physiological Parameters with Split-Root Nutrient Solution Culture

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Association between carotid lesions evaluated by Doppler color echocardiography and cardiovascular risk factors in the elderly. Preliminary results

BACKGROUND: The valuation of the extracranial carotid by echo color-Doppler takes on an extraordinary importance for the prevention of cerebral ictus at geriatric age. In this "naturalistic" study a population of old people (> 65 yrs) of Cagliari's province was considered in order to: 1) discriminate the lesions of the carotid that are imputed to atherosclerotic disease by anatomic changes of the arterial wall caused by aging; 2) study relations between lesions of the carotid and cardiovascular risk factors. METHODS: The carotids of 50 old subjects were studied by echo color-Doppler and the lesion classified in different classes of severity, according to the hemodynamic standard, comparing them with the presence of the most important cardiovascular risk factors. Hypercholesterolemia was the most frequent risk factor (76%), followed by hypertension (62%), over-weight (54%) and smoking (42%). Moreover a diffused intima-media thickening (IMT) was constant in all the subjects with values > 0.75 mm; athero-sclerotic plaques were even present in 39 subjects which only in 4 cases could be considered at risk of cerebral ischemia. RESULTS: A significant correlation between the severity of the lesions and levels of total cholesterol and LDL cholesterol for the male sex emerged, while for smoking only a trend of correlation has been obtained. CONCLUSIONS: Considering this experience it is suggested that in old subjects the presence of a diffused IMT with values > 0.75 mm must be considered as a marker of aging of the arterial wall of the carotid and not as a cardiovascular risk factor as reported in the literature for the middleaged.     

Age-related changes in cardiovascular response as a function of a chronic stressor and social support.

The effects of aging, chronic stress, and social support on cardiovascular functioning were examined using a cross-sectional design. 36 family caregivers of Alzheimer's disease victims and 34 control Ss performed 2 active coping tasks while continuous noninvasive measures of cardiovascular activity were monitored. Results revealed that caregivers high in social support displayed typical age-related decreases in heart-rate reactivity, whereas caregivers low in social support displayed age-related increases in heart-rate reactivity. Analyses further indicated that only Ss with low social support were characterized by age-related increases in systolic blood pressure. These results suggest that social support can moderate age-related changes in cardiovascular functioning, particularly in Ss exposed to a chronic stressor. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Serum calcium, magnesium, copper and zinc and risk of cardiovascular death

OBJECTIVE: To study the association of serum calcium, magnesium, copper and zinc concentrations with cardiovascular mortality. DESIGN: A nested case-control study within a prospective population study. SUBJECTS AND METHODS: 230 men dying from cardiovascular diseases and 298 controls matched for age, place of residence, smoking and follow-up time. Mean follow-up time was 10 years. Serum calcium, magnesium, copper and zinc concentrations were determined from samples kept frozen at -20 degrees C. RESULTS: High serum copper and low serum zinc concentrations were significantly associated with an increased mortality from all cardiovascular diseases and from coronary heart disease in particular. The relative risk of coronary heart disease mortality between the highest and lowest tertiles of serum copper and zinc were 2.86 (P = 0.03) and 0.69 (P = 0.04), respectively. Adjustment for social class, serum cholesterol, body mass index, hypertension and known heart disease at baseline examination did not materially alter the results. No significant differences were observed in concentrations of serum calcium and magnesium between cases and controls. CONCLUSIONS: High serum copper and low serum zinc are associated with increased cardiovascular mortality whereas no association was found with serum calcium and magnesium and mortality risk.