Dose-response relationship of elements with blood lipids and the potential interaction: A cross-sectional study from four areas with different pollution levels in China

Dyslipidemia is a common metabolic disorder, characterized by elevated levels of triglycerides (TG), total cholesterol (TCH) and low-density lipoprotein cholesterol (LDL-C), as well as decreased level of high-density lipoprotein cholesterol (HDL-C)[1]. It is a well-established risk factor for cardiovascular disease, accounting for more than half of the worldwide cases of coronary artery disease [2], [3]. Abnormally elevated LDL-C concentration is associated with low bone mass and increases fracture risk [4]. In recent years, a growing number of studies also supported that high TG and low HDL-C levels could play a relevant role in inducing the occurrence and progression of diabetic kidney disease [5], [6]. According to the data released by the Global Burden of Disease Collaborative Network, high LDL-C accounted for 4.4 million deaths and a 41% increase in disability-adjusted life-lost years (DALYs) in 2019[7]. Notably, the overall prevalence of dyslipidemia is on the rising in China, increasing from 18.6% in 2002 to 43% in 2014 and is estimated to reach 27.5% by 2060 in the United States [8], [9]. Therefore, exploration of the risk factor as well as effective prevention strategy has become a public health priority worldwide.

Dyslipidemia is considered as multifactorial metabolic disorder and the potential pathogenesis is related to genetics, lifestyle and environmental factors [10], [11]. In recent years, the impact of environmental exposure has received increasing concern. Some studies found that metal elements such as lead, mercury and zinc were related to changes in blood lipids as well as the risk of dyslipidemia. A community-based investigation among Chinese old people found that the odds ratio (OR) (95% confidence interval, CI) of dyslipidemia was 1.86 (1.23–2.80) in participants with the highest quartile of blood lead level compared with the lowest quartile, which was consistent with the result of National Health and Nutrition Examination Survey (NHANES), 2005–2016 [12], [13]. In addition, blood mercury level was positively correlated with the increase in serum lipid levels and the risk of dyslipidemia based on a nationally representative survey in Korea [14]. In real scenarios of simultaneous exposure to multiple elements, the combined effect may become weakened, enhanced and even reversed as compared to the individual effect, depending on whether an antagonistic or synergic effect exists among elements. A study from China reported that the individual effect of Zinc was positive on dyslipidemia while the combined effect with other elements became negative [15]. However, few studies investigated the potential interaction of elements on dyslipidemia.

With the growing number of people using selenium supplements, the influence on blood lipids has attracted widespread attention. Several epidemiological investigations reported that blood selenium was positively related to dyslipidemia, and the ORs of elevated TG, TCH, LDL-C as well as decreased HDL-C increased among individuals with higher circulating selenium levels [16], [17]. On the contrary, a survey consisting of 140 elderly Chinese found that participants with higher selenium at baseline showed decreased levels of TCH and TG while a increased level of HDL-C after 7 years of follow-up [18]. Similar discrepancies also existed in the studies of cobalt and blood lipids [19], [20]. These were probably due to the difference in element exposure levels in each study. In fact, an exposure-response curve covering a broad exposure range is vital to understand continuous blood lipid changes responding to element load [21]. At the same time, it could provide valuable evidence for threshold setting, contributing to the prediction and prevention of dyslipidemia.

Based on data from a cross-sectional study in Hunan province, China, which was previously reported elsewhere[22], a total of 23 elements in plasma were measured by inductively coupled plasma mass spectrometry (ICPMS), including aluminium (27Al), titanium (including two isotopes 47Ti and 48Ti), vanadium (51V), chromium (52Cr), manganese (55Mn), iron (56Fe), cobalt (59Co), nickel (60Ni), copper (63Cu), zinc (66Zn), arsenic (75As), selenium (78Se), rubidium (85Rb), strontium (88Sr), molybdenum (95Mo), cadmium (111Cd), tin (118Sn), antimony (121Sb), barium(137Ba), tungsten (182W), thallium (205Tl), lead (208Pb) and uranium(238U), and we aimed to explore the association between 23 plasma trace elements and 4 blood lipid markers, including the potential interaction and dose-response relationship.

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