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. Author manuscript; available in PMC: 2007 Jul 20.
Published in final edited form as: J Nutr Biochem. 2006 Dec 4;18(7):482–487. doi: 10.1016/j.jnutbio.2006.09.004

Factors associated with longitudinal plasma selenium decline in the elderly: The EVA Study

Josiane Arnaud 1,2,*, Tasnime N Akbaraly 3, Isabelle Hininger 1, Anne-Marie Roussel 1, Claudine Berr 3
PMCID: PMC1913201  PMID: 17142028

Abstract

Selenium status decreases in elderly populations. Cardiovascular diseases are the primary cause of death in French elderly and selenium may protect against cardiovascular diseases. The present work aims to evaluate the relationships between cardiovascular related risk factors and plasma selenium variability in an elderly population during a nine-year period. 751 subjects from the EVA (“Etude du Vieillissement Artériel”) study, aged 59 to 71 at baseline were followed for 9 years. Clinical examinations and life style questionnaires were repeated every two years. Plasma selenium determinations were performed at baseline and at the end of the study. The association between the nine-year plasma selenium variability and studied risk factors at baseline or occurring during the follow-up was evaluated by using multivariate linear regression models. After controlling all potential associated factors, age of subjects (p<0.01), obesity (p=0.02) and occurrence of cardiovascular disease during follow-up (p=0.03) increased the longitudinal decline in plasma selenium, whereas gender, education, smoking, alcohol intakes, dyslipidemia, diabetes, hypertension had no effect (p>0.05). It may be postulated that obesity and occurrence of cardiovascular events are the main factors associated to plasma selenium fall during ageing. The respective roles played by nutritional and metabolism changes in the mechanism of these associations still need to be explored.

Keywords: selenium decline, elderly, cardiovascular diseases, cardiovascular disease risk factors

Introduction

Selenium is an essential trace element mainly involved in redox balance as part of glutathione peroxidases, thioredoxine reductase and selenoprotein P but also, more specifically, in cerebral function as part of selenoprotein P [1], thyroid function as part of iodine deiodinases, as well as in immune functions [2]. In the elderly, selenium status decreases slightly compared to younger adults as long as subjects are healthy but dramatically drops when subjects are institutionalised or ill [3,4]. Recent epidemic logical studies have suggested that an adequate selenium status in the elderly is associated with a lower mortality rate [5, 6] and a lower incidence of age related pathology [2, 6–10], possibly due to oxidative stress deleterious effect in ageing [11, 12]. Therefore, maintaining an adequate selenium status in the elderly may be of importance, particularly in Europe, where selenium intakes are low compared to recommended dietary daily intake, optimal glutathione peroxidase activity or immune functions [2, 3, 13, 14].

Cardiovascular diseases are the primary cause of death in France [15, 16] and low serum selenium concentrations have been reported to increase cardiovascular mortality and morbidity although the protective role of selenium against cardiovascular diseases remains debated [2]. Repeated measurements of plasma selenium concentration, a good biological indicator to evaluate selenium status [17], were performed on participants of the EVA study (“Etude du Vieillissement Artériel”); a nine-year longitudinal study whose aim was to examine determinants of cognitive and cardiovascular functions in a French elderly population [18].

In contrast to previous publications, the present work deals with the relationships between longitudinal plasma selenium variability during this study and main cardiovascular risk factors, cardiovascular disease occurrence or life style at baseline, as well as changes in health status or life style occurring during the nine-year follow-up.

Methods and Materials

Study population

From 1991 to 1993 (EVA0), 1389 volunteers (574 men and 815 women, mean age: 65; range: 59–71) residing in the town of Nantes (Western France) were recruited from electoral rolls, and to a lesser extent, via information campaigns. During the last follow-up of the EVA study (EVA6), between June 2000 and December 2001, blood sampling was obtained for 773 subjects. The present analysis is restricted to the 751 subjects (455 women and 296 men) who had a plasma selenium determination, both at baseline and at the end of the study, and focuses on the relationships between cardiovascular risk factors or cardiovascular disease occurrence and longitudinal plasma selenium variability. The study protocol was approved by the Ethical Committee of the University Center Hospital of Kremlin-Bicêtre (Paris). Signed informed consent was obtained from all participants at enrolment.

Questionnaire and medical examination

At baseline (EVA0) and at the end of the study (EVA6), a general questionnaire allowed us to obtain information on socio-demographic factors such as sex, age, educational achievement, marital status and tobacco and alcohol consumption habits. Alcohol consumption was determined from the subject’s estimated average amount of alcoholic beverages ingested weekly and expressed in g alcohol/day. In addition, height and weight were measured and body mass index (BMI) was calculated. Two independent measures of systolic and diastolic blood pressure were made with a digital electronic tensiometer after a 10-minute rest.

Biological variables

At baseline and at the end of the study blood samples were drawn between 8.30 am and 9.30 am after a 12-hour fast. Biological procedures for the determination of cholesterol and glucose levels have been described elsewhere [19]. Plasma selenium was determined by electrothermal atomic absorption spectrometry (Perkin Elmer 5100) according to a previously described method [20]. The spectrometer was fitted with a Zeeman background correction, a platform pyrolytical furnace and an electrodeless discharge lamp (EDL). Plasma was 5 fold diluted in a solution containing 0.2% Triton X100 and 0.1 mol nitric acid, and 15 μg platinum was used as a matrix modifier. Selenium concentration was obtained using standard addition calibration. Precision, expressed as within and between run coefficient of variations stood at 1.4 % and 1.8% respectively. Accuracy was checked by using Seronorm® trace element serum as an internal quality control (Sero®, Billingstad, Norway) and the tolerance limits were ±10 % of the batch target value in use. In addition, the laboratory took part in two external quality assessment schemes and its annual scores were acceptable (values higher than 60%).

Statistical analysis

The characteristics of subjects at baseline were compared between two groups: those who had the two measurements of selenium at baseline and at the end of the study (complete assessment, n=751) and those who did not (n=658). Results were expressed by percentage and means with their standard deviation (SD). To test differences between these two groups, Chi square test and Student’s t-test were used. The characteristics at baseline and at the end of the follow-up of the 751 subjects who had the two plasma selenium measurements were also compared.

Plasma selenium concentrations at baseline and at the end of the study and corresponding plasma selenium differences were normally distributed and were analysed as continuous variables. Multivariate linear regression models were used to analyse factors associated to longitudinal plasma selenium variability. The first model studied the association between the studied factors at baseline and plasma selenium variability. In this model were included the following parameters: sex, age, education (no school or primary school versus high school or university) as a socio-economic level index [21], plasma selenium concentrations [22], marital status (single or not) as a loneliness index, tobacco status (current/former/non smokers), alcohol consumption (≥ 16 g versus <16 g per day [23]), obesity (BMI ≥ 30 kg/m2 [24]), hypertension (systolic or diastolic blood pressure ≥ 140 or ≥ 90 mm Hg respectively, or use of hypertensive drugs or report of hypertension medical history), diabetes (plasma glucose level ≥ 7.80 mmol/l or use of anti-diabetic drugs or report of diabetes medical history), dyslipidemia (total cholesterol ≥ 6.2 mmol/l or use of lipid-lowering drugs or report dyslipidemia medical history), and history of cardio-vascular diseases (myocardial infarction, angina pectoris, stroke or use of vascular drugs). In the second model, the association between changes in studied factors and plasma selenium variability was analyzed. The following variables were included in the model: smoking (non-smoker versus smoker or former smoker or stopped smoking during study), marital status (always versus never or becoming married during follow-up or becoming single), obesity (not obese versus obese or becoming obese or becoming non-obese), diabetic (none versus previous history or onset), hypertensive (none versus previous history or onset), dyslipidemic (none versus previous history or onset), and cardiovascular diseases (none versus previous history or new occurrence). In addition, sex, age and education as main morbidity predictors and plasma selenium concentration at baseline [22] were included. All these potential explaining variables were included simultaneously. Statistical significance was defined by a p-value < 0.05. Statistical analyses were performed using SAS software version 9.1 (SAS Institute, Inc. Cary, North Carolina).

Results

At baseline 1389 subjects were included in the EVA study. Their main characteristics have been previously described as well as the influence of the studied factors on plasma selenium concentration at baseline [10, 18]. Among them, 54.1 % (n=751) completed the study. Drop out subjects lived alone less frequently (17.2% versus 24.2%, p=0.001), were more frequently men (44.8% versus 37,9%, p=0.009) and exhibited significantly more frequently hypertension (52.8% versus 46.5%, p=0.02), and obesity (12.3% versus 9.1%, p=0.05) than the subjects who completed the study, but they did not differ for baseline plasma selenium concentration (p=0.54), age (p=0.64), education (p=0.15), smoking (p=0.06), alcohol consumption (p=0.60), dyslipidemia (p=0.51), diabetes (p=0.36) and history of cardiovascular disease (p=0.08).

Reported characteristics of the population at the beginning and after nine years are shown in table 1. At baseline, mean plasma selenium concentration was equal to 1.10 μmol/l and median was of 1.09 μmol/l. The maximum, 75th and 25th percentiles, and minimum plasma selenium values were 1.94, 1.23, 0.95 and 0.58 μmol/l respectively. At the end of the follow-up, mean (minimum-maximum) plasma selenium concentrations decreased to 1.00 (0.48–1.80) μmol/l, whereas median (25th – 75th percentiles) were of 0.99 (0,88–1.11) μmol/l. During the follow-up, 4.9% (n=24) of the subjects stopped smoking; 12.7% (n=95) became single whereas 1.7% (n=13) got married. Onset of diabetes, hypertension and dyslipemia and occurrence of cardio-vascular events were observed in 27 (3.7%), 248 (33.1%), 142 (19.3%) and 134 (17.8%) subjects respectively. In addition, 3.0% (n=17) of the participants became obese whereas BMI decreased to a value lower than 30 in 3.7% (n=21) of them. During the follow-up, a mean plasma selenium decline of 0.10 ± 0.21 μmol/l was observed and the selenium decrease was estimated at 0.006 (±0.002) μmol/l per year (p<0.0001). The maximum decrease was of 0.97 μmol/l. and the 75th percentile of the plasma selenium variation distribution was equal to 0.22 μmol/l. A decrease in plasma selenium concentration was noted in 71.8% of subjects.

Table 1.

Characteristics of the 751 subjects at baseline and the end of the study.

* Baseline End
Plasma Selenium, μmol/l Mean ± SD 1.10 ±0.20 1.00 ±0.18
Age, years Mean ± SD 65 ± 3 74 ±3
Marital status Married n 580 498
Single n 170 252
Smoking Never smokers n 298 298
Former smokers n 151 172
Smokers n 45 24
Alcohol intake g/day Median (CI) 0,6 (0–20;8) ND**
≤ 16 g/day n 525 ND**
>16 g/day n 213 ND**
Body mass index, kg/m2 Mean ± SD 25.1 ± 3.6 24.7 ± 3.7
Obesity No n 682 523
Yes n 68 47
Dyslipidemia No n 399 257
Yes n 338 485
Diabetes No n 692 665
Yes n 33 60
Hypertension No n 397 149
Yes n 353 601
Personal history of No n 688 589
cardio-vascular diseases Yes n 63 162
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*

Results are expressed either as mean ± SD (SD = standard deviation), or as median (CI) with CI = confidence interval, or n (number of subjects),

**

ND = not evaluated at the end of the study.

Results of multivariate linear regression models are presented in tables 2 and 3. Longitudinal plasma selenium decline was significantly associated with age (p<0.01). Selenium fall was also significantly associated with plasma selenium level at baseline (p<0.0001) due to the well-known regression to the mean phenomena’s [22]. No significant association was observed between plasma selenium decline and other studied factors at baseline (table 2). Association between plasma selenium decline and studied factor modification during the study is indicated in table 3. The occurrence of cardiovascular events (p=0.03) as well as lasting obesity (p=0.02) significantly increased the fall in plasma selenium. No association was found between plasma selenium decrease and the other factors taken into account.

Table 2.

Association between longitudinal plasma selenium decrease during the nine-year follow-up and risk factors measured at baseline.

Results of linear regression models adjusted on all factors listed in the table

Plasma selenium decrease
β* SD* p-value
Plasma selenium at baseline μmol/l 0.662 0.032 <0.0001
Age at baseline years 0.006 0.002 0.003
Sex Women versus men 0.014 0.018 0.41
Education ≥ high school versus ≤ primary school −0.018 0.013 0.16
Marital Status Married versus Single −0.016 0.016 0.33
Smoking Former smokers versus non smokers 0.004 0.017 0.80
Smokers versus non smokers −0.0003 0.025 0.98
Alcohol consumption >16 g/d versus ≤16 g/d 0.021 0.016 0.18
Obesity Yes versus No 0.037 0.023 0.10
Dyslipidemia Yes versus No −0.018 0.013 0.16
Diabetes Yes versus No 0.026 0.032 0.41
Hypertension Yes versus No 0.023 0.013 0.07
Personal history of cardiovascular disease Yes versus No 0.023 0.023 0.30
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*

Results of linear regression were expressed by linear regression coefficient (β) adjusted on all factors in the table, (SD: standard deviation).

Table 3.

Association between longitudinal plasma selenium decrease and changes in risk factor during the nine-year follow-up.

Results of linear regression models adjusted on all factors listed in the table

Plasma selenium decrease
β* SD* p-value
Plasma selenium at baseline μmol/l 0.664 0.041 <0.0001
Age years 0.007 0.003 0.007
Sex Women versus men 0.022 0.022 0.31
Education ≥ high school versus ≤ primary school −0.013 0.016 0.44
Marital Status Becoming married**versus Married −0.128 0.076 0.09
Single versus Married −0.007 0.021 0.73
Becoming single**versus Married 0.032 0.024 0.18
Smoking Stopped smoking**versus non-smokers 0.035 0.041 0.38
Former smoker versus non-smokers 0.037 0.022 0.09
Smoker versus non-smokers 0.034 0.044 0.43
Obesity Becoming obese**versus non-obese 0.011 0.054 0.85
Obese versus non-obese 0.088 0.038 0.02
Becoming non obese**versus non obese 0.061 0.041 0.14
Dyslipidemia Becoming dyslipemic**versus normolipemic −0.013 0.023 0.57
Dyslipemic versus normolipemic −0.017 0.019 0.35
Diabetes Becoming diabetic**versus non-diabetic 0.072 0.047 0.13
Diabetic versus non-diabetic 0.010 0.043 0.81
Hypertension Becoming hypertensive**versus normotensive −0.005 0.022 0.81
Hypertensive versus normotensive 0.011 0.021 0.59
Cardio-vascular diseases (CVD) Past history of CVD versus no history 0.001 0.045 0.98
CVD event **versus no history 0.051 0.023 0.03
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*

Results of linear regression were expressed by linear regression coefficient (β) adjusted on all factors in the table, (SD: standard deviation),

**

during the follow-up.

Discussion

Plasma selenium concentration largely depends on selenium intake and varies widely geographically [2, 9, 17]. Differences in plasma selenium concentrations between French regions have been reported in the SU.VI.M.AX study [25] and selenium status in the Nantes area is higher than in the East or the Center of France [25, 26]. The baseline plasma selenium concentrations observed in this study were similar to those reported in France in younger adults [26–28] and higher than plasma selenium concentrations reported in French institutionalized elderly populations [29, 30] in agreement with previous studies conducted in free-living elderly [3, 4]. It confirms that low plasma selenium concentrations in the elderly is especially found in those who are institutionalized [3, 4, 31], due to low intake [3, 29], reduced physical functioning [32] or severe pathologies [9] and can reflect undernutrition, lower bioavailability, increased requirements or metabolic changes. However, these values appear to be marginally lower than those necessary to achieve optimal activity of glutathione peroxidase, which occurs at plasma concentrations around 1.25 μmol/l [2, 13, 17]. Sub-optimal selenium status may increase the susceptibility to various pathologies in elderly [2, 8–10, 13].

Numerous case-control or nested-control studies report plasma selenium concentrations in cardiovascular diseases [2, 33], and its main associated risk factors such as hypertension [34, 35], dyslipidemia [36–38], diabetes [39], smoking [40, 41], alcohol abuse [40, 41] and obesity [42] and the results are conflicting. To our knowledge this is the first report which focuses on longitudinal plasma selenium variability in a random free living elderly population. We observe a significant decline in plasma selenium concentrations in free-living subjects during the 9 year-follow-up. This decrease is more pronounced in older subjects in agreement with previous cross sectional studies conducted in Europe [43–46] but it contrasts with the third National Health and Nutrition Examination Survey results [47, 48] which show similar serum selenium concentrations in adults and older people. These discrepancies may be related to difference in population characteristics. Among the studied risk factors, age, occurrence of cardiovascular diseases and obesity were pointed out as determinants of longitudinal plasma selenium decline. Smoking, alcohol consumption as well as previous history or onset of diabetes, dyslipidemia and hypertension had no significant effect on longitudinal plasma selenium decline in agreement with some previous case-control studies, which did not report any difference between cases and controls [34, 36–42, 49]. The positive relationship between age and longitudinal plasma selenium decrease observed in this study confirms the results of previous cross sectional European surveys [3, 4, 31, 43–46]. In addition, the cross sectional relationship between plasma selenium concentration and age in EVA was observed at the end (data not shown) of this study but not at baseline [18] confirming that the decline in plasma selenium with age may be delayed in free living elderly [43–45]. Cardiovascular disease occurrence during the follow-up significantly increased the longitudinal decline in plasma selenium. This observation, together with the lack of effect of previous history of cardiovascular events may contribute to the explanation of discrepancies reported in the literature [2, 33] concerning plasma selenium status and cardiovascular disease relationship and the effect of preventive selenium supplementation. Indeed, the longitudinal decline in plasma selenium concentration may be transient and linked to the significant decrease in plasma selenium reported during acute phase response [50], and therefore reflect more a consequence than a cause of the disease in people with plasma selenium concentration higher than the threshold value reported in different studies [2, 33]. Finally, our results show the adverse effect of obesity on longitudinal plasma selenium decline. Nevertheless, the association between longitudinal plasma selenium decrease and obesity became significant only in subjects with persistent obesity. This observation may contribute to explain discrepancies reported in the literature [25, 34, 37]. Obesity is associated with increased oxidative stress due to insulin resistance, accumulation of intracellular triglycerides or increase in adipokine release [51, 52] and is a well known key factor for cardio-vascular diseases [53]. Taken together, our result suggests that obese elderly may need higher antioxidant, especially selenium, intake to counteract the higher oxidative stress, which leads to vascular oxidative dysfunction.

To the best of our knowledge, this epidemiological survey is the first which studies the association between cardiovascular risk factors or cardiovascular disease occurrence and selenium longitudinal variation in an elderly population. The results highlight the role of obesity and cardiovascular events in decreasing selenium status. Nonetheless, this preliminary data must be interpreted cautiously and needs to be confirmed on other elderly populations. Moreover, the respective importance of nutritional and metabolism changes in the mechanism of these associations still need to be explored.

Footnotes

Grants, sponsors and funding sources: The EVA (“Etude du Vieillissement Artériel”) study was carried out under an agreement between INSERM and the Merck, Sharp and Dohme-Chibret Laboratories (WestPoint, PA) and was supported by EISAI laboratory (France). N. Tasnime Akbaraly was supported by a grant from the French Alzheimer’s disease Association.

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