Eum et al. between lead and conduction disturbances. expected, tibia and patella lead levels increased tibia lead was associated with the develop- Therefore, we did not include hypertension with age and lower education levels. Tibia lead ment of QT prolongation and JT prolonga- or HDL-C in our primary analyses. Results correlated highly with patella lead (Spearman tion (Table 3). Compared with those in the were similar to the main analyses, however, correlation coefficient = 0.62), and both tibia lowest tertile of tibia lead, those in the high- when we additionally adjusted for hyperten- and patella lead correlated moderately with est had an OR of 2.53 (95% CI, 1.22–5.25; sion (defined as physician’s diagnosis, sys- blood lead (Spearman correlation coefficients: p-trend = 0.003) for the development of QT tolic blood pressure ≥140 mmHg or diastolic tibia = 0.29; patella = 0.34). Those subjects for prolongation and 2.53 (95% CI, 0.93–6.91; blood pressure ≥ 90 mmHg) at baseline or whom we had data from a second ECG meas- p-trend = 0.04) for the development of JT HDL-C. We also examined models with the urement (n = 496) did not differ in age-ad- prolongation, after adjusting for covariates. additional covariates physical activity (meta- justed levels of tibia (mean = 21.2 µg/g), patella There was a paradoxical reduction in odds bolic equivalents), dietary intake of n-3 fatty (mean = 29.8 µg/g), or blood lead (mean = 5.8 for AV block with higher baseline tibia and acids (grams per day), and alcohol consump- µg/dL) or baseline QTc interval (mean = 394.0 patella lead, but no association otherwise with tion (≥ 2 drinks/day) and found similar results. msec) from subjects without a second ECG patella or blood lead. We used SAS (version 9.2; SAS Institute Inc., (n = 103; means: tibia, 23.7 µg/g; patella, 32.4 The results were not materially affected Cary, NC) to perform all analyses. We defined µg/g; blood, 5.9 µg/dL; baseline QTc interval, by excluding the 102 men who were tak- statistical significance as p < 0.05. 400.5 msec; all p-values for differences > 0.18). ing QT-prolongation drugs at baseline, nor Higher tibia lead was associated with signi- by including the one (patella) or six (tibia) Results ficant increases in QTc interval and QRSc men with high bone lead uncertainty values The distribution of lead exposure biomarkers duration (Table 2). Compared with those in (data not shown). When we used the alterna- by general characteristics of participants at the lowest tertile of tibia lead, participants tive definition for QT prolongation (QTc baseline is shown in Table 1. The age (mean in the highest tertile had a 7.94 msec [95% > 450 msec), a stronger estimated effect of ± SD) at the first ECG was 66.7 ± 7.0 years, confidence interval (CI), 1.42–14.45; tibia lead on QT prolongation was seen: The with an average of 8.1 ± 3.1 years between p-trend = 0.03] greater increase in QTc interval odds of QT prolongation for those in the the two ECGs. The mean ± SD tibia, patella, and a 5.94 msec (95% CI, 1.66–10.22; p-trend highest tertile compared with the lowest tertile and blood lead levels at baseline were 21.6 = 0.005) greater increase in QRSc duration of tibia lead was 3.65 (95% CI, 1.43–9.31; ± 12.0 µg/g, 30.3 ± 17.7 µg/g, and 5.8 ± 3.6 over 8 years after adjusting for covariates. There p-trend = 0.004). In sensitivity analyses only µg/dL, respectively, and the medians were 19 was no association with patella or blood lead. among men who were nonhypertensive at (IQR, 13.5–27) µg/g, 27 (IQR, 18–37) µg/g, In analyses of ECG conductance distur- baseline, we found similar association between and 5 (IQR, 3.9–7.0) µg/dL, respectively. As bances at the follow-up ECG, higher baseline tibia and patella lead and QTc interval, JTc intervals, QRSc duration, and QT and JT prolongations (data not shown). The only Table 1. Mean ± SD levels of lead exposure biomarkers by general characteristics at baseline. slight difference in results was elevated odds Tibia lead Patella lead Blood lead of arrhythmia for those in the highest ter- Baseline characteristic n (µg/g) n (µg/g) n (µg/dL) tile of tibia lead compared with those in the Age (years) lowest (OR = 2.01; 95% CI, 0.70–5.77; < 60 96 15.0 ± 8.4 96 22.4 ± 11.9 95 5.2 ± 2.9 p-trend = 0.09). 60–64 140 19.2 ± 9.1 142 26.0 ± 12.9 139 6.1 ± 4.4 65–69 175 22.5 ± 12.8 175 31.5 ± 17.5 170 6.2 ± 3.5 Discussion ≥ 70 183 26.0 ± 12.8 186 36.3 ± 21.0 185 5.7 ± 3.3 BMI (kg/m2) In this nonoccupational cohort of elderly < 25 134 21.0 ± 9.4 133 28.9 ± 14.6 132 5.5 ± 3.7 men free of cardiac conduction abnormali- 25–29 313 22.0 ± 12.3 315 31.1 ± 18.5 310 6.0 ± 3.6 ties at baseline, we found strong associa- ≥ 30 147 21.2 ± 13.5 151 29.6 ± 18.5 147 5.9 ± 3.4 tions between long-term cumulative lead Education (years) exposure, as measured by lead in tibia bone, ≤ 12 (≤ high school) 61 28.2 ± 18.9 63 38.0 ± 20.8 62 6.2 ± 3.7 and development of ECG conduction dis- 13–15 (some college) 213 22.6 ± 11.5 214 33.0 ± 19.2 211 6.1 ± 3.5 16 (college graduate) 252 20.6 ± 10.3 255 27.5 ± 15.8 249 5.6 ± 3.3 turbances. Over an average follow-up of > 16 (graduate school) 68 16.4 ± 8.1 67 24.6 ± 12.2 67 5.6 ± 4.5 approximately 8 years, higher tibia bone lead Albumin-adjusted serum calcium tertiles (mg/dL) concentration at baseline was associated with 8.38–9.31 204 20.1 ± 12.0 206 27.8 ± 17.2 201 5.4 ± 2.9 greater increase over time in QTc interval and 9.32–9.58 188 21.9 ± 11.6 190 30.2 ± 17.6 191 5.9 ± 4.0 QRSc duration. Additionally, compared with 9.61–10.82 202 22.9 ± 12.2 203 32.8 ± 18.0 197 6.2 ± 3.7 those in the lowest tertile of tibia bone lead Smoking status concentration, those in the highest tertile had Never 175 20.3 ± 11.2 175 28.5 ± 17.7 174 5.8 ± 3.4 significantly higher odds of developing QT Former 368 22.2 ± 12.5 372 31.0 ± 18.2 364 5.7 ± 3.5 Current 51 21.6 ± 10.6 52 30.7 ± 13.2 51 7.0 ± 4.5 and JT prolongation. It is unclear why there QT prolongation medication was an inverse association between bone lead Yes 100 21.9 ± 12.5 102 29.7 ± 15.1 100 6.0 ± 3.5 and AVCD. Although chance cannot be ruled No 494 21.5 ± 11.9 497 30.4 ± 18.2 489 5.8 ± 3.6 out, it is possible that survival bias contributes Diabetes to this finding. We have previously found a Yes 73 23.0 ± 11.1 74 32.7 ± 17.7 72 5.2 ± 3.0 strong association between patella bone lead No 521 21.4 ± 12.1 525 29.9 ± 17.7 517 5.9 ± 3.6 and cardiovascular mortality (Weisskopf et al. Hypertension Yes 328 22.6 ± 13.0 329 31.3 ± 18.4 325 5.8 ± 3.3 2009), which could exert a downward influ- No 266 20.4 ± 10.5 270 29.0 ± 16.7 264 5.9 ± 3.9 ence on the effect estimates found here, pos- Myocardial infarction sibly leading to the inverse association with Yes 35 21.5 ± 8.3 36 31.0 ± 16.8 35 6.7 ± 3.8 AVCD. The association with mortality was No 559 21.6 ± 12.2 563 30.2 ± 17.8 554 5.8 ± 3.6 weaker for tibia bone lead, thus a downward 942 119 | number 7 | July 2011 • Environmental Health Perspectives ovlume