We investigated the association between MS and environmental exposure to heavy metals based on the 2008 KNHANES data, which were obtained from a representative sample of the noninstitutionalized civilian population of Korea. We found that environmental factors, particularly blood lead level, as well as recognized conventional risk factors for MS significantly affected MS and its relevant pathophysiology.
Blood lead was the only heavy metal that showed a significant association with MS after adjustment for demographic and biochemical parameters. The prevalence of MS in the study subjects increased significantly according to log-transformed lead quartiles. The prevalence of moderate to high CVD risk subjects, as estimated by the Framingham risk score, also showed a significant increasing trend according to lead quartile. Moreover, the ORs of MS by lead quartile were significantly high, with trends that increased progressively according to lead quartile. Mercury, cadmium, arsenic, and other heavy metals also increased significantly in subjects with MS when the effects of confounders were not adjusted for. However, no significant differences were observed after adjustment. The other heavy metals did not demonstrate any meaningful trends in the ORs for MS when compared by quartiles. These results suggest that environmental lead exposure is closely associated with the prevalence of MS and a high CVD risk.
People can be exposed to lead through contaminated air, water, soil, food, and consumer products, and they can inhale and ingest lead . After inhalation or ingestion, lead is absorbed into the body through the mucous membranes. Environmental lead is ubiquitous, which means that most people in the world probably have trace blood lead levels . Lead exposure has decreased drastically since leaded gasoline was banned internationally and since the use of lead compounds began to decline in the 1970s. However, substantial amounts of lead are still utilized in industrial products . About 15% of the lead to which a person is exposed is absorbed into the body; however, children, pregnant women, and patients with calcium, zinc, or iron deficiencies are likely to absorb much more [20, 21]. Lead accumulates in the blood, soft tissues, and bone. Small amounts of lead are stored in the brain, spleen, kidneys, liver, and lungs [17, 22]. Lead that has accumulated in the body is eliminated very slowly through the urine and is also excreted through the stool, nails, and sweat . The estimated half-life of lead in bones is 20–30 years, and these organs could be a source of lead continuously released into the bloodstream . The half-life of lead in the blood of adults is about 40 days. However, blood lead has a longer half-life in children and pregnant women, as their bones are rapidly remodeled, which translates into increased blood levels of lead . Generally, blood lead levels are measured to evaluate lead exposure, but the total amount of accumulated lead in the body is not accurately reflected by this measurement . The World Health Organization and the U.S. Centers for Disease Control and Prevention announced that blood lead levels > 10 μg/dL may affect health [20, 24]. However, the definitive level for safe exposure to lead has not yet been identified, because blood lead levels < 10 μg/dL can also cause health problems [20, 24].
Chronic lead exposure is detrimental to health. Chronic exposure to low-level lead can cause depletion of glutathione and protein-bound sulfhydryl groups, resulting in an increase in reactive oxygen species and damage to cell structures, including DNA and cell membranes . Chronic lead exposure inhibits DNA transcription, vitamin D synthesis, and the function of enzymes that maintain cell membrane integrity. Lead also alters the permeability of blood vessels and the synthesis of collagen . Additionally, lead can have harmful effects on immune system development and cause production of excessive inflammatory proteins . As a result, lead may cause an increase in levels of proinflammatory mediators and lipid peroxidation, suppress nitric oxide levels, change calcium homeostasis, as well as alter autonomic function and heart rate variability, which, in turn, could increase the likelihood of hypertension and CVD [25, 28].
Another remarkable finding of this study was that serum triglyceride level was the only diagnostic component of MS significantly associated with blood lead level in multiple linear regression analysis. Some researchers have found that acute or chronic lead exposure does not greatly change triglyceride levels, or may even reduce levels [29, 30]. However, direct comparison of our results with investigations that focused on subjects living in areas with high endemic lead concentrations is not appropriate. A previous experimental study also reported that lead exposure causes hypertriglyceridemia, and the VA Normative Aging Study, a population-based study performed to investigate the effects of low-level lead exposure, reported similar results to our study [25, 31].
Our study has some limitations. First, as KNHANES 2008 was a cross-sectional study, a causal relationship between heavy metals and MS cannot be determined. Second, the heavy metal exposure status was evaluated only by blood samples, not by bone or soft tissue samples. As a result, the measurements may not accurately reflect chronic exposure status. Third, MS is defined as a cluster of insulin resistance-associated components, such as abdominal obesity, dyslipidemia, hypertension, and hyperglycemia, and it is not clear whether MS should be regarded as a single disease entity . Despite these limitations, our study results are meaningful, because they revealed a significant association between blood lead concentration and MS in a large number of subjects representative of the entire Korean population. All study subjects underwent accurate heavy metal analyses with strict quality controls, and a significant association between blood lead level and MS was identified after adjusting for demographic and social characteristics. Furthermore, because previous studies have already revealed that MS is closely related to high CVD risk, MS should be a useful clinical target for treatment, regardless of debate regarding its definition [33–35]. In fact, many clinical practice guidelines recommend MS management, and some communities and countries have been actively conducting intervention campaigns to prevent and manage MS [10, 36]. Thus, our finding that low-level lead exposure is a risk factor for CVD is meaningful.