Results of this review show that the higher values of serum selenium, including those in the high normal range, are associated with hypertension, but high levels of trace elements copper or zinc and low levels of any of these trace elements are not. The association of high serum selenium levels with hypertension persisted after adjustment of various confounding factors. In addition, the results of quantile regression indicate that the effect of per unit increments in serum selenium’s on hypertension was stronger with diastolic blood pressure compared to systolic blood pressure (Figures 2 and 3). Interestingly, this finding also supports the study by Mark et al. where a group of nutritionally deprived population was supplemented with dietary selenium and the population developed diastolic but not systolic hypertension [37]. Although several studies suggest a potential role of copper and zinc in hypertension, this study did not show an association.
This study’s findings support previous studies reporting higher daily selenium intake in U.S. population than the rest of the world. Its results extend those of an earlier NHANES study (2003–2004), showing a positive association of serum selenium with hypertension [16], by having a larger sample size, a later and longer time period, a more inclusive age range of 8 to 80 years, and accounting for potential confounding factors, and using the precise evaluation of cut off points in serum trace elements in more recent and clinically relevant AHA hypertension guidelines. The association of higher serum selenium levels, irrespective of the participant’s anti-hypertensive medicine intake further strengthens the association.
Findings show higher levels of serum selenium are associated with hypertension, including the high normal range, but not associated with either high or low levels of copper and zinc. Also, the results of quantile regression indicate that the effect of per unit increments in serum selenium’s on hypertension was stronger with diastolic blood pressure compared to systolic blood pressure (Figures 2 and 3). This finding is comparable with the findings by Mark et al. where a group in a nutritionally deprived population was supplemented with dietary selenium and the population developed diastolic but not systolic hypertension [34]. The finding that the increments in selenium values were observed with stable increments in total serum cholesterol over all the quantiles of serum selenium suggests the possibility of selenium accumulation with consumption of high cholesterol containing food, which are also good sources of selenium, such as eggs and meat, causing uniform association with hypertension, in both the serum selenium and serum cholesterol concurrently[35]. Also, the selenium association may be stronger than indicated, since it was found irrespective of using hypertensive medication.
Although several of the published studies suggested physiological role of serum copper and zinc with hypertension, this study did not show any correlation of hypertension with serum copper and serum zinc [18, 19, 20, 21, 22, 25, 27, 28, 29]. The incidental finding of the association of the low serum copper with hypertension on lower quantile versus higher quantile was not proven by subsequent polynomial logistic regression procedure after adjusting for confounding factors. However, a larger sample size could reveal different results with a more focused and controlled studies. Cellular and animal models need to be done in serum copper and serum zinc to ascertain their influence in blood pressure regulation. Moreover, it is essential to study the physiological effects of these trace elements on hypertension because several commercially available nutritional supplements include these trace elements in various proportions, which might lead to inadvertent effects in blood pressure in hypertensive population taking such nutritional supplements with high amounts of trace elements.
Although not the main objective of the study, the analysis also found a significant positive correlation of high blood pressure among smokers and males while there was a significant negative correlation of hypertension with pregnancy (Figure 1). Also, high sodium intake was not associated with hypertension as expected, presumably because normotensives were consuming high sodium diets compared to hypertensives, who were probably restricting their sodium intake [37]. Studies showed that the total parenteral nutrition patients in hospitals and chronic malnutrition are more likely to develop selenium deficiency which could be replenished by food or supplements rich in selenium [35, 37]. Since there are few publications about the metabolism and excretion of selenium, no definitive predictions can be made regarding its physiology and excretion mechanism. Therefore, avoiding selenium sources in food and water is the only method advisable to gain lower levels of selenium in blood. More focused and controlled studies including animal models need to be done to confirm the pathogenesis of hypertension linked with higher blood selenium levels at a molecular and cellular level.
Limitations:
One limitation of this study is the inclusion criteria of the hypertensive patients, where hypertensive cases were defined according to their blood pressure at examination, irrespective of their hypertension medications intake. Any participants who were taking anti-hypertensives would have potentially contributed as confounding factors in this study, if they were excluded from hypertensives group because of their normal blood pressure at examination. Also, any participant with usually normal blood pressure also would have been included as hypertensive, if blood pressure values were temporarily high during examinations. Although a recent publication showed protective role of selenium for stroke, whether the selenium is a protective factor for stroke despite its association with hypertension is still unanswered [10].