Urinary tungsten and incident cardiovascular disease in the Strong Heart Study: An interaction with urinary molybdenum

Abstract

Background: Tungsten (W) interferes with molybdenum (Mo) binding sites and has been associated with prevalent cardiovascular disease (CVD). We evaluated if (1) W exposure is prospectively associated with incident CVD and (2) the association between urinary W levels and incident CVD is modified by urinary Mo levels.

Methods: We estimated multi-adjusted hazard ratios (HRs) for incident CVD outcomes by increasing W levels for 2726 American Indian participants in the Strong Heart Study with urinary metal levels measured at baseline (1989-1991) and CVD events ascertained through 2008.

Results: Increasing levels of baseline urinary W were not associated with incident CVD. Fully-adjusted HRs (95% CIs) of incident CVD comparing a change in the IQR of W levels for those in the lowest and highest tertile of urinary Mo were 1.05 (0.90, 1.22) and 0.80 (0.70, 0.92), respectively (p-interaction = 0.02); for CVD mortality, the corresponding HRs were 1.05 (0.82, 1.33) and 0.73 (0.58, 0.93), respectively (p-interaction = 0.03).

Conclusions: The association between W and CVD incidence and mortality was positive although non-significant at lower urinary Mo levels and significant and inverse at higher urinary Mo levels. Although prior cross-sectional epidemiologic studies in the general US population found positive associations between urinary tungsten and prevalent cardiovascular disease, our prospective analysis in the Strong Heart Study indicates this association may be modified by molybdenum exposure.

Keywords: American Indians; Cardiovascular disease; Molybdenum; Strong Heart Study; Tungsten.

Fig. 1.

Hazard ratio (95% confidence interval) of CVD mortality by an increase in log transformed urinary tungsten concentration corresponding to the interquartile range (75th to 25th percentile; 0.18 µg/L) within subgroups. Hazard ratios were calculated by using age as the time metric with late entries corresponding to age at baseline, stratified by study center (Oklahoma/Arizona/North and South Dakota), and fully adjusted for sex (male/female), urinary creatinine, education (≤ 12 yrs / > 12 yrs), BMI (continuous), low-density lipoprotein (continuous), hypertension (binary), diabetes (binary), eGFR (continuous), smoking (current/former/never), urinary Mo levels (log-transformed continuous), and urinary iAs levels (logtransformed continuous).

Fig. 2.

Hazard ratio (95% confidence interval) of incident CVD by an increase in log transformed urinary tungsten concentration corresponding to the interquartile range (75th to 25th percentile; 0.18 µg/L) within subgroups. Hazard ratios were calculated by using age as the time metric with late entries corresponding to age at baseline, stratified by study center (Oklahoma/Arizona/North and South Dakota), and fully adjusted for sex (male/female), urinary creatinine, education (≤ 12 yrs / >12 yrs), BMI (continuous), low-density lipoprotein (continuous), hypertension (binary), diabetes (binary), eGFR (continuous), smoking (current/former/never), urinary Mo levels (log-transformed continuous), and urinary iAs levels (log-transformed continuous).