There are some overlapping mechanistic concerns with respect to past exposure to lead, the current obesity epidemic, and a looming increase in incidence of Cardiometabolic syndrome. Widespread environmental exposures to lead (Pb) have been greatly ameliorated in the U.S. and overall blood Pb levels for children have progressively diminished in recent decades. However past Pb exposure appears to be associated with persistent adverse effects with respect to cardiovascular disease (CVD) in adults, and Pb may exacerbate some of the metabolic disruptions that are associated with Cardiometabolic syndrome.
Environmental Pb exposure has been associated with hypertension, and compromised renal and neurological functions, but exposure to Pb has been largely overlooked as a direct risk factor for CVD. A recent systematic review and meta-analysis of epidemiological studies found that non-occupational exposure appears to be associated with a near-linear increase for risk of CVD. That association was independent of exposures to arsenic, cadmium, and copper. A prospective 20 year follow-up study of adults > 20 years of age (NHANES-III, n= 14,289) revealed that blood lead levels (BLLs) below 5 μg/dL at baseline contributed statistically CVD and ischemic heart disease mortalities. The data analysis adjusted for an extensive array of potential confounders. Similar to findings regarding BLLs and IQ scores for children, the steepest increase in CVD risk for adults was found across the lower BLLs.
The aforementioned epidemiological efforts would likely have been more revealing had life-long retention of Pb been estimated via K x-ray fluorescence. It is well established that Pb accumulates in bone even in children, and the half time for Pb in bone is very long. It is also acknowledged that bone Pb is slowly released back into blood, and that rate of “endogenous re-exposure” increases with enhanced bone resorption that occurs with aging and changes in hormonal status. Accelerated bone demineralization is also affected by sedentary lifestyle and positive caloric balance, which is also associated with excessive visceral adiposity and cardiometabolic disorders.
Excessive visceral adiposity (VAT) is causally associated with cardiometabolic disorders and chronic low-grade inflammation, and recent evidence indicates that Pb may also contribute to inflammation in the body. Aggregation of immune cells in VAT, and Pb ions both effectuate increased proinflammatory cytokines and reactive oxygen/nitrogen species (ROS/RNS) that may be associated with endothelial cell dysfunction, oxidation of LDL, and platelet activation. Excessive formation of the ROS radical superoxide may decrease the local availability of nitric oxide (NO), which is the vascular endothelium-derived relaxation factor that plays a key role in the local regulation of blood flow, blood pressure, and thrombus formation. The interaction of superoxide with NO produces peroxynitrite, which can perpetuate the production of excess ROS and proinflammatory cytokines via activation of NFkB. Those effects are likely enhanced in the presence of excessive VAT because VAT is associated with hypoadiponectinemia, and adiponectin imparts anti-inflammatory, anti-oxidative, antidiabetic, and vascular protective effects.
Exposure to Pb may exacerbate inflammation and oxidative damage that is associated with Cardiometabolic syndrome. Clinical consideration of past exposure to Pb and accelerated bone demineralization may be warranted for some patients who may be caught up in the current surge of excessive adiposity.