Abstract
Previous studies on the correlation between serum selenium and hypertension have yielded inconsistent results. Our previous analysis of participants from the National Health and Nutrition Examination Survey (NHANES) 2011–2018 indicated that elevated serum selenium concentrations were associated with an increased risk of metabolic abnormalities in obese individuals, with the primary effect being on blood pressure in males. The aim of this study was to further elucidate the relationship between serum selenium and the risk of hypertension in obese males. In this study, we examined the correlation between serum selenium concentrations and hypertension in 2,585 male participants with a body mass index (BMI) ≥ 30 kg/m2 aged between 20 and 80 years from the 2011–2018 NHANES database. The associations between serum selenium levels and hypertension were evaluated through weighted generalized linear regression analyses. To examine the saturation threshold effect between serum selenium and hypertension, a generalized additive model (GAM) and a two-piecewise linear regression model were employed. Furthermore, the saturation threshold effect was evaluated separately in subgroups stratified by BMI and age. The weighted prevalence of hypertension (51.84%) was slightly higher than that of nonhypertension (48.16%) in the participants included in this study. After rigorous adjustment for sociodemographic, physical, and laboratory test covariates, the weighted odds ratio (OR) of hypertension increased by 103% for every 1 standard deviation (SD) increase (approximately 24.41 µg) in the serum selenium concentration in participants assigned to the highest serum selenium group (weighted OR = 2.03; 95% CI = 1.24–3.32; P = 0.013). A calculation was subsequently performed to determine the saturation threshold effect of selenium on hypertension among participants in the medium and highest selenium concentration subgroups. The findings indicated that participants with serum selenium concentrations exceeding the saturation threshold (2.56 µM) demonstrated an elevated risk of developing hypertension (weighted OR = 9.58; 95% CI = 2.74–33.46; P = 0.000) in comparison to those with serum selenium concentrations below the threshold. Subgroup analyses demonstrated that serum selenium concentrations exceeding the saturation threshold were associated with an increased risk of hypertension in participants with a BMI ≤ 35 kg/m2 (weighted OR = 9.11; 95% CI = 1.43–58.24; P = 0.030) or those aged less than 55 years or younger (weighted OR = 8.37; 95% CI = 1.71–40.94; P = 0.014). For obese adult males who require additional selenium supplementation to enhancing their overall health and well-being, it is strongly recommended that the serum selenium concentrations be monitored throughout the course of supplementation to ensure that they remain within the relatively safe range (approximately less than 215.75 µg/L).
Supplementary Information
The online version contains supplementary material available at 10.1038/s41598-025-85343-1.
Keywords: Serum selenium, Z-score, Hypertension, Body mass index (BMI), Obesity, National Health and Nutrition Examination Survey (NHANES)
Subject terms: Environmental sciences, Health care, Medical research
Introduction
Hypertension is a significant contributor to cardiovascular disease and premature mortality worldwide1. Although the use of antihypertensive medications has led to a slight decrease in the global average blood pressure over the past half-century, the prevalence of hypertension has unfortunately increased2. A correlation has been demonstrated between body mass index (BMI) and both systolic and diastolic blood pressure3,4. Obesity can result in hypertension through a number of pathophysiological processes, including the activation of the sympathetic nervous system, the renin-angiotensin-aldosterone system, oxidative stress, and inflammation5. If left untreated, hypertension can cause severe complications such as stroke, renal failure, and myocardial infarction. These complications can result from cardiovascular, cerebrovascular, or renal diseases. Therefore, obesity not only increases the risk of developing hypertension but also complicates its management6.
The development of hypertension is a complex process influenced by a multitude of factors, including dietary habits. Elevated intakes of sodium, fat, and refined carbohydrates have been associated with an increased risk of developing hypertension7. Recently, the importance of trace elements in the regulation of blood pressure has also attracted increased attention8,9. Selenium is a naturally occurring chemical element that is involved in the synthesis of selenoproteins in combination with essential amino acid derivatives, including selenocysteine and selenomethionine (SeMet)10. The latter is involved in a variety of important physiological processes, such as antioxidant stress, lipid metabolism, inflammation, and immunity10,11. Appropriate levels of selenium have been demonstrated to reduce lipid peroxidation, protein carbonyls, LDL cholesterol, and atherosclerotic indices, while simultaneously increasing plasma glutathione and nitric oxide levels12.
Initial evidence of a correlation between selenium and hypertension was observed in patients with Keshan disease. This is a highly prevalent condition in areas of China with severe selenium deficiencies in the soil and diet. The primary symptoms observed included hypertension, heart failure, and pulmonary edema. However, the aforementioned symptoms can be alleviated through the administration of selenium13. Nevertheless, recent research has indicated that elevated levels of selenium are associated with decreases in glucose and insulin resistance, increases in gluconeogenesis and fasting glucose, and increases in systolic BP and diastolic BP, which may contribute to the development of cardiac dysfunction14–16. Selenium intake above the recommended daily intake may not be beneficial and may cause hypertension, diabetes and hyperlipidemia17,18. The effects of diets and supplements containing selenium on cardiovascular risk factors and events remain a topic of discussion because of the dual pro-oxidant and antioxidant properties of selenium18,19.
Obesity is a known risk factor for atherosclerosis, especially hypertension6. In our previous study, we demonstrated that selenium intake or status was associated with an increased risk of metabolic abnormalities in obese individuals. In the present study, we conducted a cross-sectional study using a representative sample from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018 to examine whether serum selenium is associated with an increased risk of hypertension in males with obesity. The aim of this study was to determine the influence of the serum selenium concentration on blood pressure abnormalities in obese males from non-selenium-deficient regions.
Methods
Study population
The NHANES is a cross-sectional survey that assesses the health and nutritional status of a nationally representative sample of noninstitutionalized individuals from the U.S. general civilian population. The survey included a series of questionnaires; physical examinations; household interviews covering demographic, dietary, and health-related questions and examinations; and laboratory tests20,21. Further information on the planning, conduct, and design of the survey can be found on the official website (https://www.cdc.gov/nchs/nhanes/ about_nhanes.htm).
In this study, we selected 10,948 obese males aged 20–85 years from the 39,056 participants included in the NHANES data from 2011 to 2018. After the exclusion of 6,686 participants with a BMI less than 30 kg/m2, 648 with undocumented BMI data, 1,013 with missing serum selenium data, and those with serum selenium concentrations (7 participants) and a BMI (9 participants) not falling within the mean ± 5 standard deviation (SD) range, the final analysis included 2,585 participants. The process for screening the study individuals is described in Fig. 1. All participants in the NHANES 2011–2018 provided informed consent, and the study protocol was approved by the NCHS Ethics Review Board.
Fig. 1.
Flow chart of the study participants.
Measurement of serum selenium concentrations
Serum samples were processed, stored, and shipped to the National Center for Environmental Health and Centers for Disease Control and Prevention for analysis. Quality control protocols were developed and distributed by the National Center for Environmental Health to all contracted laboratories. Serum selenium concentrations were quantified via inductively coupled plasma-mass spectrometry, a multielement analytical technique based on quadrupole ion chromatography-mass spectrometry technology. The instructions for sample collection, processing, and quality assessment can be accessed on the NHANES website.
(https://wwwn.cdc.gov/Nchs/Nhanes/2011-2012/PBCD_G.htm; https://wwwn.cdc.gov/Nchs/Nhanes/2013-2014/PBCD_H.htm; https://wwwn.cdc.gov/Nchs/Nhanes/2015-2016/PBCD_I.htm;
Assessment
The data set included information on the demographic characteristics of the participants, including age, sex, race (non-Hispanic white, non-Hispanic black, non-Hispanic Asian, Mexican American, and other races), marital status (married and living with a partner; widowed, divorced, and separated; never married), education (college and above, high school, less than high school), family size (1–3 people, 4–6 people and more than 7 people), and annual family income (< $45,000, $45,000-$99,999, and ≥ $100,000). The physical examination data collected included measurements of standing body mass index (BMI, kg/m2), waist circumference (cm), systolic blood pressure (SBP, mmHg) and diastolic blood pressure (DBP, mmHg). Furthermore, laboratory data, including blood glucose (mM), glycohemoglobin (HBA1C; %), triglyceride (TG; mM), total cholesterol (TC; mM), high-density lipoprotein cholesterol (HDL-C; mM), low-density lipoprotein cholesterol (LDL-C; mM), hemoglobin (Hb; g/L), urine acid (UA; µM), and urea nitrogen (BUN; mM) levels, the urinary albumin-to-creatine ratio (uACR; mg/g), albumin (g/L), urine albumin (mg/L), and serum sodium (Na+; mM) and serum iron (Fe2+; µM), were obtained.
The questionnaire was utilized to collect data regarding the smoking history of the participants, who were subsequently classified into three categories: never, former, and current smokers. Additionally, the participants were queried about their status with respect to alcohol consumption (never, former, and current), with responses from current drinkers converted to reflect their weekly alcohol intake. The final exposure categories were as follows: never, former, mild (defined as one exposure per week), moderate (one to three exposures per week), and vigorous (more than 3 exposure per week).
The term “physical activity (PA)” encompasses both work and recreational activities. This definition is detailed in a previous report22. Briefly, the level of PA was determined via the PA Questionnaire from the NHANES, which is based on metabolic equivalent (MET) values, the type of activity, the weekly frequency of participation in the activity, and the duration of the activity. The activity scores were calculated in accordance with the following formula: PA = MET×weekly frequency×duration of each physical activity. Participants with a PA score of 0 were classified as exhibiting no PA (defined as “no”), whereas those with a PA score of ≥ 1 were classified as engaging in some PAs (defined as “yes”).
The data regarding dietary selenium and daily energy intake were obtained from two reliable 24-hour dietary recall interviews. The participants were requested to provide a detailed account of all the food consumed over the preceding 24-hour period up until the time of the interview at the mobile examination center (MEC). The staff subsequently calculated the quantity of each nutrient consumed by the participants on the basis of the information provided. The mean intake of selenium and energy from the two 24-hour dietary recall interviews was employed as the foundation for the final estimate.
Definition criteria for hypertension
The MEC conducted blood pressure measurements, which included measurements of systolic and diastolic BP. Hypertension was defined as meeting any of the following diagnostic criteria: (1) a mean SBP of 140 mmHg or greater; (2) a mean DBP of 90 mmHg or greater; (3) self-reported hypertension; or (4) the use of antihypertensive medication. The participants’ questionnaire responses provided this information. The International Society of Hypertension has established guidelines that set a threshold of 140/90 mmHg.
The protocol used to calculate the average blood pressure was as follows: in the case where all diastolic BP readings were zero, the average was zero. If only one blood pressure reading was taken, that reading was considered the average. However, if there was more than one blood pressure reading, the first reading was always excluded from the average.
Statistical analysis
The appropriate weighting methods were employed to account for the complex sampling design, thereby ensuring that the results were provided in accordance with the guidelines set forth by the NHANES23. The fundamental attributes of categorical variables were quantified as 95% confidence intervals (CIs) of survey-weighted percentages (%), whereas those of continuous variables were expressed as survey-weighted means (95% CIs). The discrepancies between continuous variables were examined via survey-weighted linear regression, whereas the differences between categorical variables were analyzed by a survey-weighted chi-square test.
The objective of the present study was to investigate the association between serum selenium and hypertension while controlling for potential confounding factors that influence blood pressure. The distribution of selenium based on population characteristics was examined. A weighted generalized linear regression model was used to assess the independent association between serum selenium and hypertension in obese males. This study employed three levels of adjustment. Model 1 was adjusted for sociodemographic variables. Model 2 was adjusted for clinical characteristics and blood biochemical tests, whereas Model 3 was additionally adjusted for the covariates from Models 1 and 2.
Smooth curves were fitted via a generalized additive model. A log-likelihood ratio test was conducted to compare the single line model with the two-piecewise linear regression model, with the objective of determining the existence of a saturation threshold. The inflection point (K), which connects the line segments, was identified as the maximum likelihood value calculated via the recursive algorithm method. Moreover, the potential correlation between serum selenium and hypertension, on either side of the inflection point, was reassessed through the use of weighted generalized linear modeling.
The statistical analyses were conducted by using R (http://www.R-project.org) and Empower Stats (http://www.empowerstats.com, X&Y Solutions, Inc., Boston, MA). A two-tailed P value less than 0.05 was considered to indicate statistical significance.
Research ethics
The NHANES study protocols used were approved by the Research Ethics Review Board of the National Center for Health Statistics. The methods were conducted in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. Written informed consent was obtained from all study participants.
Results
Baseline characteristics of the participants
The study population consisted of 2,585 participants aged 20 to 80 years who met the specific inclusion and exclusion criteria. A total of 1,446 participants were diagnosed with hypertension, resulting in a weighted prevalence of 51.84%. Table 1 presents the weighted distributions of sociodemographic characteristics and other covariates for selected participants on the basis of the serum selenium tertiles. The ranges of the selenium tertiles were as follows: T1 (< 2.34 µM), T2 (2.34–2.58µM), and T3 (> 2.58 µM). Significant differences were detected between the selenium tertiles, except age (P = 0.113), marital status (P = 0.698), family size (P = 0.125), family income (P = 0.072), smoking status (P = 0.420), work activity (P = 0.656), recreational activity (P = 0.833), alcohol consumption (P = 0.408), BMI (P = 0.723), waist circumference (P = 0.516), glucose (P = 0.338), HBA1C (P = 0.273), HDL-C (P = 0.224), LDL-C (P = 0.580), SBP (P = 0.539), urinary albumin (P = 0.713), and UA (P = 0.815) levels, uACR (P = 0.380), daily selenium intake (P = 0.232) and energy intake (P = 0.491). The participants in the highest tertile of serum selenium were more likely to be non-Hispanic White, either married or living with a partner, and to reside in households with a relatively small number of individuals and a higher level of education. Additionally, the T3 group presented elevated levels of TC, TG, Hb, albumin, serum Fe2+, serum Ca2+ and DBP. In contrast, the BUN levels were significantly lower in this group than in the other groups (all P < 0.05).
Table 1.
Weighted characteristics of the study participants based on the serum selenium concentration.
| Characteristic | Serum Selenium (Se) concentration tertiles | P value | ||
|---|---|---|---|---|
| T1 (Se < 2.34 µM) |
T2 (Se 2.34–2.58 µM) |
T3 (Se > 2.58 µM) |
||
| Selenium (µM) | 2.17 (2.15, 2.18) | 2.46 (2.45, 2.46) | 2.81 (2.78, 2.83) | < 0.000 |
| Age (Years) | 49.13 (47.43, 50.83) | 46.84 (45.39, 48.29) | 47.75 (46.47, 49.03) | 0.113 |
| Race/Ethnicity (%) | 0.000 | |||
| Non-Hispanic White | 61.41 (54.82, 67.60) | 66.07 (61.00, 70.79) | 69.66 (64.48, 74.38) | |
| Non-Hispanic Black | 14.53 (11.42, 18.32) | 10.58 (8.19, 13.57) | 8.50 (6.51, 11.02) | |
| Non-Hispanic Asian | 1.30 (0.87, 1.92) | 2.45 (1.76, 3.41) | 1.69 (1.14, 2.50) | |
| Mexican American | 9.90 (7.41, 13.12) | 12.97 (9.67, 17.19) | 10.86 (7.74, 15.05) | |
| Others | 12.86 (9.77, 16.76) | 7.92 (5.81, 10.72) | 9.29 (7.23, 11.86) | |
| Marital Status (%) | 0.698 | |||
| Married/Living with partner | 69.83 (64.23, 74.89) | 66.42 (60.00, 72.29) | 69.65 (64.30, 74.52) | |
| Widowed/Divorced/Separated | 13.72 (10.82, 17.24) | 16.18 (12.58, 20.58) | 12.84 (9.61, 16.95) | |
| Never married | 16.46 (12.45, 21.43) | 17.39 (13.74, 21.78) | 17.51 (14.10, 21.54) | |
| Education (%) | 0.032 | |||
| Collage and above | 54.03 (48.21, 59.74) | 62.60 (57.61, 67.33) | 63.11 (57.97, 67.97) | |
| High school | 29.52 (24.87, 34.63) | 24.04 (20.20, 28.34) | 24.77 (20.88, 29.12) | |
| Less than high school | 16.45 (13.39, 20.05) | 13.37 (10.87, 16.34) | 12.12 (9.78, 14.94) | |
| Family Size (%) | 0.125 | |||
| 1–3 people | 67.70 (62.35, 72.61) | 71.13 (66.84, 75.06) | 64.54 (60.24, 68.62) | |
| 4–6 people | 30.34 (25.65, 35.49) | 26.07 (22.20, 30.36) | 32.60 (28.54, 36.93) | |
| More than 7 people | 1.96 (1.05, 3.64) | 2.80 (2.06, 3.80) | 2.86 (2.08, 3.93) | |
| Family income (%) | 0.072 | |||
| < $45,000 | 41.03 (35.29, 47.01) | 42.53 (37.48, 47.74) | 37.84 32.73, 43.24) | |
| $45,000-$99,999 | 30.63 (25.42, 36.39) | 37.62 (31.99, 43.61) | 36.93 (31.90, 42.26) | |
| ≥$100,000 | 28.35 (23.05, 34.31) | 19.85 (15.47, 25.09) | 25.23 (20.45, 30.70) | |
| Smoking (%) | 0.420 | |||
| Never | 45.20 (40.28, 50.22) | 50.34 (45.01, 55.66) | 49.46 (45.29, 53.64) | |
| Former | 36.98 (32.59, 41.60) | 31.52 (26.72, 36.74) | 35.25 (31.11, 39.62) | |
| Now | 17.82 (14.54, 21.65) | 18.15 (15.08, 21.67) | 15.15 (12.39, 18.40) | |
| Alcohol user (%) | 0.408 | |||
| Never | 6.91 (4.75, 9.94) | 4.57 (3.14, 6.62) | 4.86 (3.56, 6.59) | |
| Former | 12.76 (10.10, 16.01) | 9.95 (7.30, 13.43) | 11.54 (8.95, 14.76) | |
| Mild | 42.01 (36.97, 47.22) | 40.74 (36.44, 45.17) | 41.97 (35.79, 48.40) | |
| Moderate | 10.80 (7.78, 14.81) | 16.36 (12.83, 20.62) | 14.67 (11.07, 19.20) | |
| Heavy | 27.52 (22.72, 32.89) | 28.38 (23.97, 33.24) | 26.97 (21.35, 33.43) | |
| Work Activity (%) | 0.656 | |||
| No | 46.94 (41.91, 52.03) | 44.01 (40.14, 47.95) | 44.20 (39.04, 49.49) | |
| Yes | 53.06 (47.97, 58.09) | 55.99 (52.05, 59.86) | 55.80 (50.51, 60.96) | |
| Recreational Activity (%) | 0.833 | |||
| No | 49.91 (45.17, 54.56) | 48.73 (44.20, 53.28) | 48.00 (42.60, 53.45) | |
| Yes | 50.09 (45.35, 54.38) | 51.27 (46.72, 55.80) | 52.00 (46.55, 57.40) | |
| BMI (kg/m2) | 35.06 (34.52, 35.60) | 34.95 (34.47, 35.44) | 35.25 (34.77, 35.72) | 0. 723 |
| Waist circumference (cm) | 117.0 (115.4, 118.6) | 116.7 (115.4, 117.9) | 117.8 (116.4, 119.2) | 0.516 |
| HB (g/L) | 14.73 (14.61, 14.85) | 15.15 (15.05, 15.25) | 15.38 (15.29, 15.48) | < 0.000 |
| Glucose (mM) | 5.98 (5.78, 6.18) | 6.03 (5.84, 6.22) | 6.16 (5.97, 6.36) | 0.338 |
| HBA1C (%) | 5.87 (5.79, 5.96) | 5.87 (5.78, 5.96) | 5.96 (5.87, 6.05) | 0.273 |
| TC (mM) | 4.79 (4.67, 4.92) | 4.84 (4.74, 4.95) | 5.12 (5.01, 5.22) | 0.000 |
| TG (mM) | 1.99 (1.81, 2.18) | 2.27 (2.11, 2.44) | 2.47 (2.35, 2.60) | 0.000 |
| HDL-C (mM) | 1.15 (1.12, 1.18) | 1.12 (1.09, 1.16) | 1.11 (1.08, 1.14) | 0.224 |
| LDL-C (mM) | 2.84 (2.69, 2.99) | 2.96 (2.83, 3.09) | 2.96 (2.83, 3.10) | 0.580 |
| SBP (mmHg) | 127 (126, 129) | 126 (125, 127) | 127 (126, 128) | 0.539 |
| DBP (mmHg) | 74 (73, 76) | 75 (74, 76) | 76 (75, 78) | 0.035 |
| Albumin (g/L) | 41.73 (41.32, 42.15) | 42.54 (42.20, 42.88) | 43.19 (42.94, 43.44) | < 0.000 |
| Urine Albumin (mg/L) | 63.95 (33.75, 94.15) | 52.79 (35.71, 69.88) | 50.18 (32.33, 68.03) | 0.713 |
| UA (µM) | 379.16 (371.22, 387.09) | 378.71 (370.17, 387.24) | 382.01 (375.69, 388.34) | 0.815 |
| BUN (mM) | 5.51 (5.36, 5.65) | 5.31 (5.18, 5.44) | 5.22 (5.09, 5.35) | 0.022 |
| uACR (mg/g) | 53.31 (29.98, 76.65) | 50.98 (31.30, 70.65) | 38.09 (23.25, 52.94) | 0.380 |
| Serum Na+ (mM) | 139.41 (138.97, 139.84) | 139.73 (139.31, 140.15) | 139.31 (138.94, 139.68) | 0.030 |
| Serum Ca2+ (mM) | 2.32 (2.31, 2.33) | 2.34 (2.33, 2.34) | 2.35 (2.34, 2.36) | 0.000 |
| Serum Fe2+ (µM) | 15.42 (14.75, 16.10) | 16.13 (15.56, 16.69) | 16.39 (15.89, 16.89) | 0.052 |
| Selenium (µg) | 131.70 (126.34, 137.06) | 130.5 (125.22, 135.78) | 136.69 (132.03, 141.34) | 0.232 |
| Energy (Kcal) | 2546.9 (2448.1, 2645.7) | 2462.9 (2359.5, 2566.4) | 2535.3 (2442.4, 2628.1) | 0.491 |
| Hypertension | 0.134 | |||
| No | 48.98 (42.29, 53.69) | 50.91 (46.94, 54.87) | 45.08 (40.22, 50.02) | |
| Yes | 51.02 (46.31, 55.71) | 49.09 (45.13, 53.06) | 54.92 (49.98, 59.78) | |
Notes: Data in the table: For continuous variables: survey-weighted means (95% CI) and P values were obtained via survey-weighted linear regression (svyglm); for categorical variables: survey-weighted percentages (95% CI) and P values was were obtained via the survey-weighted chi-square test (svytable). Abbreviations: Hemoglobin, HB; Body mass index, BMI; Glycohemoglobin, HBA1C; Total cholesterol, TC; Triglycerides, TG; HDL cholesterol, HDL-C; LDL cholesterol, LDL-C; Systolic blood pressure, SBP; Diastolic blood pressure, DBP; Urine acid, UA; Urea nitrogen, BUN; Urine Albumin Creatine Ratio, uACR.
Higher serum selenium levels are associated with hypertension
Three weighted multiple regression models were constructed for the purpose of evaluating the association between the serum selenium Z-score and hypertension in males with obesity, as illustrated in Table 2. The results demonstrated that the correlation between the serum selenium Z-score and hypertension incidence was not statistically significant in either the crude model or the model adjusted for various covariates. The continuous selenium variable was subsequently transformed into a categorical variable comprising three tertiles. The results indicated that the association between the selenium Z-score and hypertension was identified in the highest tertiles of selenium. After full covariate adjustment, the weighted OR for the highest selenium tertile group in Model III was 2.03 (95% CI = 1.24–3.32; P = 0.013), indicating that obese males with serum selenium concentrations exceeding 2.58 µM (approximately 203 µg/L), presented an elevated risk of hypertension, with an observed increase of 103% for each SD (approximately 24.4 µg/L) increase in the serum selenium concentration.
Table 2.
Weighted multivariate regression analysis for the association between serum selenium and hypertension.
| Selenium, (µM) | Crude model | Adjust model I | Adjust model II | Adjust model III | ||||
|---|---|---|---|---|---|---|---|---|
| Weighted-OR (95% CI) | P value | Weighted-OR (95% CI) | P value | Weighted-OR (95% CI) | P value | Weighted-OR (95% CI) | P value | |
| Per 1 SD increase | 1.05 (0.94, 1.18) | 0.393 | 1.12 (0.98, 1.29) | 0.106 | 1.16 (0.92, 1.47) | 0.192 | 1.21 (0.92, 1.59) | 0.167 |
| Tertiles | ||||||||
| T1 (< 2.33) | 0.93 (0.60, 1.44) | 0.743 | 0.88 (0.69, 1.11) | 0.260 | 1.08 (0.80, 1.48) | 0.608 | 0.96 (0.69, 1.34) | 0.816 |
| T2 (2.34–2.58) | 1.04 (0.48, 2.25) | 0.919 | 1.29 (1.04, 1.60) | 0.021 | 1.29 (0.92, 1.82) | 0.158 | 1.59 (0.99, 2.56) | 0.079 |
| T3 (> 2.58) | 0.96 (0.72, 1.28) | 0.804 | 1.22 (0.99, 1.49) | 0.064 | 1.23 (0.69, 2.20) | 0.484 | 2.03 (1.24, 3.32) | 0.013 |
Notes Table: Survey-weighted OR (95% CI) P-value.
Outcome: Hypertension.
Exposure: Selenium.
The unadjusted model was adjusted for: none.
The adjusted I model was adjusted for: age; race; marital status; family size; education and family income.
The adjusted II model was adjusted for: BMI; waist circumference (cm); TC; TG; LDL-C; HB; HBA1C; UA; BUN; uACR; urine albumin; serum Na+; serum Fe+; recreational activity; work activity; alcohol use and smoke.
Model adjusted for: BMI; waist circumference (cm); TC; TG; LDL-C; HB; HBA1C; UA; BUN; uACR; urine albumin; serum Na+; serum Fe+; recreational activity; work activity; alcohol use and smoking; age; race; marital status; education and family size.
Higher serum selenium levels are associated with hypertension
Three weighted multiple regression models were constructed for the purpose of evaluating the association between the serum selenium Z-score and hypertension in males with obesity, as illustrated in Table 2. The results demonstrated that the correlation between the serum selenium Z-score and hypertension incidence was not statistically significant in either the crude model or the model adjusted for various covariates. The continuous selenium variable was subsequently transformed into a categorical variable comprising three tertiles. The results indicated that the association between the selenium Z-score and hypertension was identified in the highest tertiles of selenium. After full covariate adjustment, the weighted OR for the highest selenium tertile group in Model III was 2.03 (95% CI = 1.24–3.32; P = 0.013), indicating that obese males with serum selenium concentrations exceeding 2.58 µM (approximately 203 µg/L), presented an elevated risk of hypertension, with an observed increase of 103% for each SD (approximately 24.4 µg/L) increase in the serum selenium concentration.
A nonlinear relationship between the serum selenium concentration and hypertension
A segmented regression analysis was subsequently conducted, in which a distinct line segment was used to fit each selenium concentration interval. A log-likelihood ratio test was conducted to compare the one-line (nonsegmented) model to the segmented regression model, with the objective of ascertaining the serum selenium saturation threshold for participants assigned to the T2 and T3 groups. The results of the log-likelihood ratio test indicate the existence of a segmental relationship between the serum selenium concentration and hypertension, as illustrated in Fig. 2A and detailed in Table 3. The recursive algorithm was used to calculate the inflection point (K), which was determined to be 2.56 µM (approximately 201.6 µg/L).
Fig. 2.
Association between serum selenium concentration and hypertension incidence. A. A nonlinear saturation threshold association between the serum selenium concentration and hypertension was found via a generalized additive model (GAM) (P<0.05). The red line represents the smooth curve fit between the variables. The blue bands represent the 95% confidence intervals (CIs) of the fits. All the analyses were adjusted for BMI; waist circumference (cm); TC, TG, HDL-C, LDL-C, HB, HBA1C, UA, and BUN levels; uACR; urine albumin, serum Na+, serum Ca2+, and serum Fe+ concentrations; recreational activity; work activity; alcohol use and smoking; age; race; marital status; education; and family size. B. Associations between the selenium threshold segment and the risk of hypertension in different BMI subgroups. The graph shows the smoothed curve fit, with the red line representing a BMI less than or equal to 35 kg/m2, and the light green line representing a BMI greater than 35 kg/m2. C. Effect of the selenium threshold segment on the risk of hypertension, as categorized by age. The graph displays the smoothed curve fit, with the red line representing an age less than or equal to 55 years; and the light green line representing an age greater than 55 years.
Table 3.
Threshold effect analysis of increased serum selenium concentration on hypertension incidence.
| Characteristic | Participants (OR (95% CI), P value) |
|---|---|
| Fitting by standard linear model | 3.06 (1.27, 7.37) 0.0124 |
| Fitting by two-piecewise linear model | |
| Inflection point (K) | 2.56 |
| < 2.56 | 0.05 (0.00, 1.16) 0.062 |
| > 2.56 | 9.58 (2.74, 33.46) 0.000 |
| Log-likelihood ration | 0.007 |
Notes.
Table: OR (95% CI) P value.
Outcome: Hypertension.
Exposure: Selenium > 2.34 µM.
Adjusted covariates: BMI; waist circumference (cm); TC; TG; LDL-C; HB; HBA1C; UA; BUN; uACR; urine albumin; serum Na+; serum Fe+; recreational activity; work activity; alcohol use and smoking; age; race; marital status; education and family size.
Stratified analysis of the correlation between the saturation threshold of selenium and hypertension incidence
BMI is an independent risk factor for hypertension. The population was subsequently divided into two groups on the basis of BMI, with a cutoff point set at 35 kg/m2. The application of a smoothed curve fitting to the subgroup revealed a U-shaped relationship between the selenium concentration and hypertension when the BMI was less than 35 kg/m2 (Fig. 2B). As illustrated in Table 4, the serum selenium concentrations of the participants whose selenium concentrations exceeded 2.34 µM were subjected to a segmental fitting process through the application of a generalized linear model. The results indicated that for each increase of 1 µM in the serum selenium concentration exceeding the saturation threshold of 2.56 µM the weighted ORs of participants with hypertension increased by 4.50 (P = 0.034). In particular, participants with a BMI of 35 kg/m2 or less exhibited a weighted OR of developing hypertension that increased by 811% with each increase of 1µM in the selenium concentration when the serum selenium concentration exceeded the threshold (OR = 9.11, 95% CI = 1.43–58.24 P = 0.030).
Table 4.
Weighted generalized linear analysis of the associations between the selenium threshold segment and hypertension categorized by BMI.
| Selenium, µM | BMI ≤ 35 | BMI > 35 | All participants | |||
|---|---|---|---|---|---|---|
| Weighted-OR (95% CI) | P value | Weighted-OR (95% CI) | P value | Weighted-OR (95% CI) | P value | |
| Per 1 µM increase | 7.17 (1.74, 29.55) | 0.013 | 0.53 (0.04, 7.43) | 0.63 | 2.81 (0.88, 8.98) | 0.096 |
| Selenium segment | ||||||
| < 2.56 | 2.67 (0.01, 531.64) | 0.709 | 0.00 (0.00, 48.87) | 0.264 | 0.15 (0.00, 24.31) | 0.446 |
| > 2.56 | 9.11 (1.43, 58.24) | 0.03 | 1.37 (0.04, 43.02) | 0.863 | 5.50 (1.17, 25.91) | 0.034 |
Notes.
The participants in this section had serum selenium concentrations that were equal to or greater than 2.34 µM.
Table: Weighted-OR (95% CI) P value.
Outcome: Hypertension.
Exposure: Selenium
Adjusted covariates: BMI; waist circumference (cm); TC; TG; LDL-C; HB; HBA1C; UA; BUN; uACR; urine albumin; serum Na+; serum Fe+; recreational activity; work activity; alcohol use and smoking; age; race; marital status; education and family size.
In addition, age was identified as an additional independent risk factor for hypertension. The participants were divided into two age categories: those aged ≤ 55 years and those aged > 55 years. A U-shaped relationship between selenium and hypertension was demonstrated by a smoothed curve fitting analysis when the age of the participants was ≤ 55 years (Fig. 2C). A weighted generalized linear model was employed to analyze the data on both sides of the selenium threshold, with separate analyses conducted for each side. As shown in Table 5, for each increase of 1 µM in the serum selenium concentration that exceeded the identified saturation threshold, the obese males aged younger than 55 years exhibited a 737% increase in their weighted risk of developing hypertension (OR = 8.37, 95% CI = 1.71–40.94; P = 0.014).
Table 5.
Weighted generalized linear analysis of the associations between the selenium threshold segment and hypertension categorized by age.
| Selenium, µM | Age ≤ 55 | Age > 55 | All participants | |||
|---|---|---|---|---|---|---|
| Weighted-OR (95% CI) | P value | Weighted-OR (95% CI) | P value | Weighted-OR (95% CI) | P value | |
| Per 1 µM increase | 4.71 (1.14, 19.46) | 0.039 | 2.77 (0.29, 26.70) | 0.389 | 2.81 (0.88, 8.98) | 0.096 |
| Selenium segment | ||||||
| < 2.56 | 0.32 (0.00, 190.6) | 0.72 | 0.03 (0.00, 117.5) | 0.41 | 0.15 (0.00, 24.31) | 0.446 |
| > 2.56 | 8.37 (1.71, 40.94) | 0.014 | 12.14 (0.29, 510.5) | 0.226 | 5.50 (1.17, 25.91) | 0.034 |
Notes.
The participants in this section had serum selenium concentrations that were equal to or greater than 2.34 µM.
Table: Weighted-OR (95% CI) P value.
Outcome: Hypertension.
Exposure: Selenium
Adjusted covariates: BMI; waist circumference (cm); TC; TG; LDL-C; HB; HBA1C; UA; BUN; uACR; urine albumin; serum Na+; serum Fe+; recreational activity; work activity; alcohol use and smoking; age; race; marital status; education and family size.
Discussion
Hypertension is a well-established risk factor for cardiovascular disease and mortality, affecting approximately 31.1% of adults worldwide2. Obesity has been shown to affect blood pressure in both adults and children, with a nearly linear correlation between BMI and blood pressure. In fact, for every 5% increase in body weight, there is a 20–30% increase in the risk of developing hypertension24. Our previous research has indicated that serum selenium is involved in the transition from metabolically healthy to unhealthy states among participants with normal metabolic profiles who are obese. For obese males, a curvilinear relationship was observed between the serum selenium levels and the risk of developing hypertension25. In the present study, we employed a larger sample size and a cross-sectional design using data from the 2011–2018 NHANES to ascertain the relationship between serum selenium concentrations and hypertension in male participants with obesity. The results of our study indicated that the weighted prevalence of hypertension in U.S. adult males with obesity was 51.84%, which is markedly higher than the prevalence of hypertension in the general population, with an incidence rate of 36.55%26. Furthermore, the results also demonstrated that the mean selenium concentration of obese males was 2.50 µM (min: 1.34 µM or 105.5 µg/L, max:4 µM or 315 µg/L), which was higher than that of the United States (approximately 1.74 µM or 137 µg/L)27,28 and the mean selenium concentration of residents in Europe (1.09 µM or 85.8 µg/L)29. Therefore, our findings not only corroborate the conclusion that the prevalence of hypertension in obese patients is significantly greater than that in the general population, but also suggest an association between high serum selenium and hypertension.
Despite evidence from the treatment of Keshan disease, which substantiated the role of selenium in the prevention and treatment of hypertension30, the results of other studies conducted to data on the relationship between selenium and hypertension have been inconsistent. For example, a comprehensive analysis of 25 studies involving 26,000 participants in 19 countries revealed that the relationship between selenium levels and blood pressure remains uncertain31. A further cross-sectional study conducted on 2,638 participants aged over 40 years revealed a positive correlation between higher serum selenium concentrations and a high incidence of hypertension32. The findings of a prospective cohort study conducted in China involving 13,668 participants indicate that an elevated intake of selenium is associated with a reduced risk of hypertension in individuals residing in areas with low selenium availability. Conversely, in regions with elevated selenium levels, increased selenium intake has been linked to an increased incidence of hypertension among the local population. Other evidence for the correlation between selenium levels in natural environments and the prevalence of cardiovascular disease is provided by data from Finland, Denmark, and the U.S. Salonen et al. reported that low soil selenium levels in eastern Finland constituted a significant risk factor for myocardial infarction and death from ischemic heart disease33. In a Danish cohort study, serum selenium concentrations below 1µM (approximately 79 µg/L) were associated with an increased risk of coronary heart disease in a population with no relevant past medical history34. In contrast, no correlation was detected between the serum selenium concentration and the risk of myocardial infarction in the U.S. population, which may be attributed to their relatively high serum selenium concentrations. All participants in this study had serum selenium concentrations of at least 1.34 µM. (approximately 105.5 µg/L). The findings of the aforementioned previous studies have revealed that the health implications of elevated and depleted selenium concentrations should not be assessed exclusively in the context of the serum selenium’s impact on cardiovascular health. It is therefore essential to consider the influence of selenium exposure in the surrounding living environment of the participant. This exposure may represent a significant contributing factor to the observed inconsistencies in the health effects of serum selenium in populations residing in diverse selenium-exposed environments.
In 2020, Bastola and colleagues found a significant positive association between serum selenium concentrations and hypertension based on the data from 6,683 participants in the NHANES (2011–2016). After adjusting for potential confounding covariates, a weak positive association was observed between serum selenium concentrations exceeding 1.52 µM (approximately 120 µg/L) and hypertension (OR = 1.46, 95% CI = 1.29–1.66). However, the association was more pronounced when serum selenium concentrations exceeded 1.91 µM(approximately 150 µg/L), with an odds ratio of 1.69, (95% CI = 1.32–2.17)35. A further study, which examined the relationship between serum selenium concentrations and mortality in patients with hypertension by using data from the 2003–2004 NHANES, reported a U-shaped association between serum selenium concentrations and all-cause and cardiovascular mortality. The lowest mortality rates for all-cause mortality and cardiovascular mortality were observed at serum selenium concentrations of 1.73 µM and 1.65 µM (approximately 136 µg/L and 130 µg/L), respectively36. The optimal range for serum selenium concentrations has been reported to be between 1.0 and 1.6 µM (approximately 80 and 130 µg/L)37–39. The mean serum selenium concentrations observed in the present study cohort were markedly higher than the recommended concentrations, indicating that the adverse effect of selenium on blood pressure in obese males is associated with selenium overexposure. To date, no definitive conclusions have been reached regarding the correlations between the selenium dose and cardiovascular disease parameters. This may be attributed to the impact of varying levels of dietary selenium or distinct selenium forms on the intrinsic metabolic processes of selenium in the body. Further research is needed to determine the relationships among the dose, type and duration of selenium supplementation and blood pressure and other cardiovascular disease parameters.
The development of hypertension is a complex process, with oxidative stress undoubtedly representing a pivotal factor in its pathogenesis40. The excessive production of reactive oxygen species (ROS) results in a reduction in nitric oxide bioavailability, which in turn promotes vasoconstriction and is a contributing factor to the development of arterial hypertension. Selenium is an essential component of selenocysteine (SeC), and selenoproteins containing SeC residues act as antioxidants and modulators of redox processes within the body, thereby protecting cells from oxidative stress and free radical damage41. However, excessive selenium intake may precipitate alterations in the mechanism of action of this trace element on tissues. Once the concentration of selenium reaches a specific threshold, selenium replaces sulfur in the enzyme system. These replacements can converts selenium into a pro-oxidant, thereby increasing the risk of oxidative damage to cells and tissues11. Accordingly, the US Institute of Medicine suggests a dietary selenium intake of 55–75 µg/day for adults42. The tolerable daily intake of selenium is 330 µg/day43.
Notably, the subgroup analysis demonstrated that individuals with a BMI of less than 35 35 kg/m2 or an age of less than 55 years exhibited heightened sensitivity to elevated selenium levels compared with those with a higher BMI or older age, when serum selenium concentrations exceeded the saturation threshold of 2.56 µM (approximately 201.6 µg/L). The hypothesis that we propose to explain this phenomenon is as follows: in the initial stages of obesity, when a participant’s antioxidant system is stimulated, the rational concentration of serum selenium continues to induce glutathione peroxidase activity in erythrocytes, as selenium is an essential component of glutathione peroxidase. This results in the neutralization of excess ROS or RON. Thus, young males or mildly obese males whose erythrocyte glutathione activity remains high do not require excessive selenium intake to engage in the antioxidant process. An excess of selenium may instead compete with sulfur in the enzyme system, converting it into a pro-oxidant and thereby increasing the risk of abnormal fluctuations in blood pressure. As obesity progresses and the degree of obesity increases, excess adipose tissue continues to alter the process of selenium absorption, distribution, metabolism, and excretion in the body, affecting the bioavailability of selenium and limiting its function. Concurrently, the body’s antioxidant capacity diminishes with age, which renders older obese individuals potentially less responsive to the consequences of elevated serum selenium levels.
In addition, the form of selenium intake also warrants consideration. Selenium present in foods and dietary supplements exists in both organic and inorganic forms. Organic selenium is typically present in the form of sulfur-containing amino acid analogs, particularly SeMet and selenocarbon. The most prevalent chemical form of selenium in the diet is SeMet, which is among the most efficacious organic selenium compounds for enhancing the selenium status because of its capacity for nonspecific incorporation into proteins. In the liver, SeMet is metabolized to selenide, which is subsequently utilized for the synthesis of selenoproteins. These proteins play a role in regulating various biological functions in the body, including modulating the inflammatory response, antioxidant properties, and immune cell proliferation or differentiation11,44. In contrast, inorganic selenium is predominantly found in selenium salts, such as selenates or selenites45, which represent the primary form of selenium supplementation. In addition to considering the chemical form of the trace element, assessing its bioavailability and mode of administration is essential46. Compared with inorganic selenium, organic selenium, particularly SeMet, is more bioavailable and offers a greater range of benefits than inorganic selenium when it is consumed orally in conjunction with a balanced diet47,48.
The present study is not without certain potential limitations. First, this study exclusively examined the impact of selenium on blood pressure alterations in obese males, and did not consider the potential influence of other minerals or trace elements. Second, all participants in this study were obese; thus, the study did not control for the potential influence of dietary and genetic factors on the outcomes. Third, as an epidemiological investigation, this study confirmed the correlation between elevated serum selenium concentrations and an increased risk of hypertension. The present study used the serum selenium concentrations as a means of assessing selenium status in the body, rather than relying on calculations of dietary selenium intake or the specific forms of selenium present. This is a consequence of the inherent limitations of cross-sectional studies. Accordingly, further prospective clinical studies are needed to complement and refine the existing evidence regarding whether this association is directly causal. However, the study also has several notable strengths. First, the sample size of this study was sufficiently large. Second, the study employed the recommended methodology for weighting and combining data, asset by the NHANES, thus facilitating a more comprehensive examination of the moderating impact of varying serum selenium concentrations on blood pressure alterations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Author contributions
B.L and M.H contributed to the conception of the study; Y.Y and C.J analyzed and interpreted the data; H.S prepared the initial manuscript draft；Y.L supervised the revision of the manuscript; All authors reviewed and approved the final version of the manuscript.
Funding
This work was supported by funding from the Shenzhen Science and Technology Program (JCYJ20220530151201002), and Shenzhen High-Level Hospital Construction Fund.
Data availability
The NHANE survey included a series of questionnaires; physical examinations; household interviews covering demographic, dietary, and health-related questions and examinations; and laboratory tests . Further information on the planning, conduct, and design of the survey can be found on the official website (https://www.cdc.gov/nchs/nhanes/ about_nhanes.htm).The instructions for sample collection, processing, and quality assessment can be accessed on the NHANES website (https://wwwn.cdc.gov/Nchs/Nhanes/2011-2012/PBCD_G.htm; https://wwwn.cdc.gov/Nchs/Nhanes/2013-2014/PBCD_H.htm; https://wwwn.cdc.gov/Nchs/Nhanes/2015-2016/PBCD_I.htm; https://wwwn.cdc.gov/Nchs/Nhanes/2017-2018/PBCD_J.htm).
Declarations
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The NHANE survey included a series of questionnaires; physical examinations; household interviews covering demographic, dietary, and health-related questions and examinations; and laboratory tests . Further information on the planning, conduct, and design of the survey can be found on the official website (https://www.cdc.gov/nchs/nhanes/ about_nhanes.htm).The instructions for sample collection, processing, and quality assessment can be accessed on the NHANES website (https://wwwn.cdc.gov/Nchs/Nhanes/2011-2012/PBCD_G.htm; https://wwwn.cdc.gov/Nchs/Nhanes/2013-2014/PBCD_H.htm; https://wwwn.cdc.gov/Nchs/Nhanes/2015-2016/PBCD_I.htm; https://wwwn.cdc.gov/Nchs/Nhanes/2017-2018/PBCD_J.htm).