Purpose: Deposition of lead into bone offers a better method over conventional blood lead measurement to discern long-term lead exposure and its insidious accumulation within the body. Bone lead deposition has been identified as an independent risk factor for hypertension (HTN). Yet, little is known how bone lead as a risk factor for HTN can be translated into clinical utility. We examined the association between bone lead levels and resistant-HTN.
Methods: All subjects were males, participating in the Veterans Affairs Normative Aging Study (NAS) with an age variation of 48-93 years old. Participants were included if there was complete data on HTN (systolic blood pressure, diastolic blood pressure, and anti-HTN medication), lead (blood, bone-patella, bone-tibia), as well as demographic and confounding variables. Cases of resistant-HTN were identified by meeting criteria for a) inadequate SBP (≥140 mmHg) or DBP (≥90 mmHg) on 3 medications or b) requiring ≥ 4 medications for blood pressure control. Resistant-HTN was categorized as a dichotomous variable, based upon meeting the noted criteria, while tibia and patella bone lead were treated as continuous variables. The data was analyzed using a binomial logistic regression, accounting for demographic and confounding variables.
Results: Of the 871 total study participants, 111 cases of resistant-HTN (12.7%) were identified. Amongst the cases of resistant-HTN, the mean tibia and patella lead levels were 23.1 μg/g and 31.5 μg/g, respectively. Both mean levels were higher than those among the participants without resistant-HTN (21.5 μg/g and 30.9 μg/g, respectively). Tibia lead levels demonstrated a significant association with resistant-HTN (OR=1.27 (95% CI, 1.01-1.59) per one IQR increase in tibia lead (15μg/g), p=0.04) after adjusting for age, BMI, cigarette pack-year burden, income, education, and ethnicity. A weak, non-significant association was observed between patella lead and resistant-HTN (OR = 1.16 (95% CI, 0.92-1.46) per one IQR increase in patella lead (21μg/g), p=0.21).
Conclusion: Lead has been long-studied for its effect on blood pressure. Yet, lead has not previously been assessed for the role it plays in clinical outcomes. Difficulty in attaining goal blood pressure may be influenced by environmental exposures. Our study demonstrates an increased association between tibia lead and resistant-HTN status, with an OR of 1.27 per one IQR increase in tibia lead. Tibia lead represents a novel risk factor for resistant-HTN. Future research should consider screening and mitigation strategies for populations with resistant-HTN exposed to long-term low-levels of lead.