Cadmibel : design CADMIum in BELgium Study Cross-sectional study 1985 - 1989 Aim: to study the health effects of environmental exposure to cadmium Research partners: K.U.L. - U.C.L. - Université de Liège - Institute of Hygiene and Epidemiology, Brussels, Universiteit Hasselt
Cadmibel : design Fieldwork –home visits: anthropometry, blood pressure, questionnaire on medical history, life style, etc. –24 h urine sample: Cd, As, Ca, creatinine, retinol- binding protein, ß2-microglobulin, N-acetyl-ß- glucosaminidase, albumin, amino acids –whole blood: Cd, Pb, Se, ZPP –serum: Zn, creatinine, ß2-microglobulin
PheeCad : design Public Health and Environmental Exposure to CADmium Study Prospective follow-up study of Cadmibel: 1991-’94 Aim: How does exposure change over time ? Additional measurements on bone metabolism and calcium homeostasis Hard endpoints
Cadmibel : exposure to cadmium PollutedReference MEN Blood Cd, nmol/L11.08.5*** Urinary Cd, nmol/24h10.27.9*** WOMEN Blood Cd, nmol/L11.08.3*** Urinary Cd, nmol/24h 7.66.6*** data are geometric means; *** p<0.001
Determinants of urinary cadmium Percentage of explained variance for U-Cd MENWOMEN age (linear and squared)26.829.0 place of residence7.49.4 smoking6.33.3 past smoking 2.7n.s.
Urinary cadmium vs. cadmium in soil and vegetables Staessen et al. Lancet 1994;343:1523-7. Soil samples from kitchen gardens Vegetable samples from participants with garden
Cadmium in soil and vegetables : geometric means Characteristics controlpolluted Cd in soil, ppm0.814.86*** Cd in celery, ppm0.682.43*** Cd in leek, ppm0.671.58*** Cd in carrots, ppm0.450.98*** Cd in beans, ppm0.150.42*** Urinary Cd, nmol/24h8.49.8** ** p<0.01; *** p<0.001
Percentage of vegetables above the EU norm in the study area European legislation: maximal values are 2 mg/kg for leafy vegetables and 1 mg/kg for all others.
Cadmium in urine, soil and vegetables : correlations Correlation between Cd in soil and –Cd in celery: r = 0.77 (p=0.02) –Cd in leek: r = 0.63 (p=0.05) –Cd in carrots: r = 0.52 (p=0.15) –Cd in beans: r = 0.67 (p=0.05) Correlation between urinary Cd and –Cd in soil: r = 0.76 (p=0.01) –Cd in celery: r = 0.63 (p=0.07) –Cd in leek: r = 0.70 (p=0.03) –Cd in carrots: r = 0.57 (p=0.11) –Cd in beans: r = 0.92 (p=0.001)
PheeCad : Cd-exposure over time Since mid ‘60 : reductions in emission –change from thermic to electrolytic procedure –transport of zinc ore concentrates was covered (hangars) Since 1985 : information on risk reduction –using tap water in stead of well water –liming soil of kitchen gardens –not grow leafy vegetables
Cadmium and renal effects Cadmium and fractures Cadmium and mortality
Cadmium and renal effects Cadmium accumulates in the kidney Half-life = 10 to 20 years Urinary Cd represents life-long exposure Markers of kidney function: –tubular function: urinary excretion of NAG, RBP, ß2-microglobulin, AA, Ca
Cadmium and fractures Chronic exposure to cadmium may promote urinary calcium loss Cadmium may interfere with the metabolism of calcium, vit. D, collagen Severe cadmium poisoning is associated with ostemalacia or osteoporosis
Cadmium and bone : prospective analysis Staessen et al. Lancet 1999; 353:1140-4. n = 506 baseline exposure to cadmium after a median follow-up of 6.6 years: –incidence of fractures (questionnaire + confirmation by family physician)
Relative risk of fracture and height loss in Cox regression fractures men women N° endpoints 20 24 Cd excretion1.201.73** Polluted area2.76*4.30** Cd in soil1.39*1.54*** Cd in leek1.93*2.27** Cd in celery1.69*2.07** * p<0.05, ** p<0.01, *** p<0.001 RR for a doubling of Cd conc.; analyses adjusted for significant covariates
In postmenopausal women, urinary cadmium correlated negatively with bone density. The population-based risk for fractures in districts near the smelters was 35%. Conclusion: cadmium may promote skeletal demineralisation, which may lead to increased bone fragility and raised risk of fractures.
Rational to study hard endpoints Source: MIRA, achtergronddocument: verspreiding van zware metalen, 2004
Hard-end points: study in progress 17 year of follow-up Causes of mortality (national institute of statistics) Incidence of diseases (general practioner) Endpoints of interest: total mortality, total cancer and lung cancer mortality.* *based on evidence from IARC