BackgroundEnvironmental exposure to cadmium decreases bone density indirectly through hypercalciuria resulting from renal tubular dysfunction.ObjectiveWe sought evidence for a direct osteotoxic effect of cadmium in women.MethodsWe randomly recruited 294 women (mean age, 49.2 years) from a Flemish population with environmental cadmium exposure. We measured 24-hr urinary cadmium and blood cadmium as indexes of lifetime and recent exposure, respectively. We assessed the multivariate-adjusted association of exposure with specific markers of bone resorption, urinary hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), as well as with calcium excretion, various calciotropic hormones, and forearm bone density.ResultsIn all women, the effect sizes associated with a doubling of lifetime exposure were 8.4% (p = 0.009) for HP, 6.9% (p = 0.10) for LP, 0.77 mmol/day (p = 0.003) for urinary calcium, –0.009 g/cm2 (p = 0.055) for proximal forearm bone density, and –16.8% (p = 0.065) for serum parathyroid hormone. In 144 postmenopausal women, the corresponding effect sizes were –0.01223 g/cm2 (p = 0.008) for distal forearm bone density, 4.7% (p = 0.064) for serum calcitonin, and 10.2% for bone-specific alkaline phosphatase. In all women, the effect sizes associated with a doubling of recent exposure were 7.2% (p = 0.001) for urinary HP, 7.2% (p = 0.021) for urinary LP, –9.0% (p = 0.097) for serum parathyroid hormone, and 5.5% (p = 0.008) for serum calcitonin. Only one woman had renal tubular dysfunction (urinary retinol-binding protein > 338 μg/day).ConclusionsIn the absence of renal tubular dysfunction, environmental exposure to cadmium increases bone resorption in women, suggesting a direct osteotoxic effect with increased calciuria and reactive changes in calciotropic hormones.

Abstract-Blood pressure variability based on office measurement predicts outcome in selected patients. We explored whether novel indices of blood pressure variability derived from the self-measured home blood pressure predicted outcome in a general population. We monitored mortality and stroke in 2421 Ohasama residents (Iwate Prefecture, Japan). At enrollment (1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995), participants (mean age, 58.6 years; 60.9% women; 27.1% treated) measured their blood pressure at home, using an oscillometric device. In multivariable-adjusted Cox models, we assessed the independent predictive value of the within-subject mean systolic blood pressure (SBP) and corresponding variability as estimated by variability independent of the mean, difference between maximum and minimum blood pressure, and average real variability. Over 12.0 years (median), 412 participants died, 139 of cardiovascular causes, and 223 had a stroke. In models including morning SBP, variability independent of the mean and average real variability (median, 26 readings) predicted total and cardiovascular mortality in all of the participants (P≤0.044); variability independent of the mean predicted cardiovascular mortality in treated (P=0.014) but not in untreated (P=0.23) participants; and morning maximum and minimum blood pressure did not predict any end point (P≥0.085). In models already including evening SBP, only variability independent of the mean predicted cardiovascular mortality in all and in untreated participants (P≤0.046). The R 2 statistics, a measure for the incremental risk explained by adding blood pressure variability to models already including SBP and covariables, ranged from <0.01% to 0.88%. In a general population, new indices of blood pressure variability derived from home blood pressure did not incrementally predict outcome over and beyond mean SBP. This article was sent to Morris J. Brown, Guest Editor, for review by expert referees, editorial decision, and final disposition. Methods Study DesignAs described in detail elsewhere, 5 from 1988 until 1995, we contacted 4969 individuals who resided in 4 districts of Ohasama, a rural community in Iwate Prefecture, Japan, and who were ≥35 years old. Residents were not eligible if they were not at home during normal working hours (n=1057) or if they were hospitalized (n=166) or incapacitated (n=94). Of the remaining 3652 residents, 3090 (84.6%) participated in baseline and follow-up examinations. The study complies with the Declaration of Helsinki, and the study protocol was approved by the institutional review board of Tohoku University School of Medicine and by the Ohasama Town Government Department of Health. Participants gave written informed consent. We excluded 669 participants from analysis because they had not measured their home blood pressure (n=218), had obtained <5 morning or evening readings (n=322), or because at enrollment they had a history of stroke (n=129). Thus, the number of participants statistically analyzed totaled 2421. Data Collection...

The improved Finapres apparatus, known as the Finometer, measures finger blood pressure noninvasively on a beat-to-beat basis and gives waveform measurements similar to intra-arterial recordings. The Finometer measures brachial pressure and corrects for finger pressure accordingly. It also corrects for the hydrostatic height of the finger with respect to the heart level. The objective was to validate the Finometer according to the revised British Hypertension Society (BHS) protocol and the criteria of the Association for the Advancement of Medical Instrumentation (AAMI). We carried out a main validation test using a subject group of 102 black women, which was also divided into smaller groups, namely 24 hypertensives, 25 obese normotensive and 35 lean normotensive women. Finometer and mercury sphygmomanometer blood pressure (BP) measurements were taken early in the morning before breakfast, after the subjects stayed overnight in a research unit. Within the whole subject group, the Finometer satisfied the AAMI criteria for accuracy and achieved an overall A/B grading according to the BHS criteria. The sphygmomanometer measurements were 128 7 20/ 78 7 12 mmHg compared to 130 7 20/78 7 11 mmHg for the Finometer. The average differences between the mercury sphygmomanometer and Finometer readings for systolic and diastolic BP were, respectively, À1.83 7 6.8 and 0.88 7 7.5. Systolic readings of the Finometer device differed by less than 5 mmHg for 64%, by less than 10 mmHg for 86% and differed by less than 15 mmHg for 96% of all readings. A total of 63% of all diastolic readings of the Finometer by less than 5 mmHg, 85% by less than 10 mmHg and 94% of all readings differed by less than 15 mmHg. On the basis of these results, the Finometer device satisfied the validation criteria of AAMI and received an A/B grading according to the BHS protocol. It can therefore be recommended for measurements in the clinical set-up and for research purposes.

During the 5 years, 24% of Africans with optimal BP developed hypertension. The surge in hypertension in Africa is largely explained by modifiable risk factors. Public health strategies should focus aggressively on lifestyle to prevent a catastrophic burden on the national health system.