Skip Navigation


European Heart Journal Advance Access first published online on January 22, 2007
This version published online on February 6, 2007
European Heart Journal, doi:10.1093/eurheartj/ehl479
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
28/5/628    most recent
ehl479v2
ehl479v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Nawrot, T. S.
Right arrow Articles by Struijker-Boudier, H. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nawrot, T. S.
Right arrow Articles by Struijker-Boudier, H. A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The European Society of Cardiology 2007. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Blood pressure and blood selenium: a cross-sectional and longitudinal population study

Tim S. Nawrot1, Jan A. Staessen1,*, Harry A. Roels2, Elly Den Hond1, Lutgarde Thijs1, Robert H. Fagard1, Anna F. Dominiczak3 and Harry A. Struijker-Boudier4

1 Studies Coordinating Centre, Laboratory of Hypertension, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases, Campus Gasthuisberg, University of Leuven, Herestraat 49, Box 702, B-3000 Leuven, Belgium
2 Unité de Toxicologie Industrielle et de Médecine du Travail, Université catholique de Louvain, Bruxelles, Belgium
3 British Heart Foundation Blood Pressure Group, Department of Medicine and Therapeutics, University of Glasgow, Glasgow, United Kingdom
4 Department of Pharmacology, Cardiovascular Research Institute, University of Maastricht, Maastricht, The Netherlands

Received 15 March 2005; revised 8 December 2006; accepted 21 December 2006.

* Corresponding author. Tel: +32 16 34 7104; fax: +32 16 34 7106. E-mail address: jan.staessen{at}med.kuleuven.be


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Acknowledgements
 References
 
AIMS: Western Europeans have low blood levels of selenium (BSe), an antioxidant trace element. In a Flemish population, we investigated the cross-sectional and longitudinal association of blood pressure (BP) with BSe.

METHODS AND RESULTS: We randomly recruited 710 subjects (mean age 48.8 years; 51.8% women). We measured BP and BSe and kept participants in follow-up for BP. At baseline, systolic/diastolic BP averaged (SD) 130/77 (17.3/9.2) mmHg. BSe was 97.0 (19.0) µg/L. Of 385 participants with normal baseline BP (<130 and < 85 mmHg), over 5.2 years (range 3.4–8.4 years), 139 developed high-normal BP (130–139/85–90 mmHg) or hypertension (≥140/90 mmHg). In multivariate-adjusted cross-sectional analyses of men, a 20 µg/L (~1 SD) higher BSe was associated with lower BP with effect sizes of 2.2 mmHg systolic (95% CI – 0.57 to – 5.05; P = 0.009) and 1.5 mmHg diastolic (95% CI – 0.56 to – 2.44; P = 0.017). In prospective analyses of men, a 20 µg/L higher baseline BSe was associated with a 37% (95% CI – 52 to – 17; P = 0.001) lower risk of developing high-normal BP or hypertension. None of these associations was significant in women.

CONCLUSION: Deficiency of selenium might be an underestimated risk factor for the development of high BP in European men.

Key Words: Blood pressure • Epidemiology • Hypertension • Prospective


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Acknowledgements
 References
 
The essential trace mineral selenium is of great importance to human health.1–4 Taken up from the soil, selenium enters the food chain. Animal protein is the main source of dietary selenium, accounting for 66% of the total selenium intake in Western Europe.5 In many parts of the world, including Western Europe, the concentration of selenium in the soil is < 0.5 p.p.m., so the risk of selenium deficiency and the associated detrimental health effects are considerable.

Selenium-dependent enzymes, such as glutathione peroxidase, maintain nitric oxide in its reduced form and protect against oxidative stress. Via this mechanism, selenium deficiency might predispose to cardiovascular disease.1,3,4 However, the scientific evidence linking cardiovascular disorders to selenium depletion remains equivocal, because most studies including all those focusing on hypertension were cross-sectional or had a case–control design, or because the published reports included only men.6–8 Some studies in humans showed association between hypertension and oxidative stress,9,10 or between blood pressure (BP), arterial stiffness, and intake of vitamin C.11 However, to our knowledge, no prospective population-based study or clinical trial ever investigated the relation between BP and the blood selenium (BSe) concentration. In the framework of the Flemish Study on Environment Genes and Health Outcomes (FLEMENGHO),12 we therefore assessed both cross-sectionally and longitudinally whether, in a random population sample, BP and the incidence of high-normal BP and hypertension were associated with BSe while adjusting for host factors and lifestyle.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Acknowledgements
 References
 
Study population and data collection
Baseline observations were collected in Belgium from 1985 to 1989.12 In six rural districts, we identified a random population sample stratified by sex and age (20–39 years vs. 40–59 years vs. ≥ 60 years) with the aim to recruit equal numbers in each group. The six municipalities provided listings of all inhabitants sorted by address. Households, defined as all subjects living at the same address, were the sampling unit. We gave households consecutive numbers and we generated a random number list by use of the SAS random function. Households with a number matching the random list were invited. Household members > 20 years were eligible, but they were no longer included in the cohort if the quota of a sex–age stratum had been met.

Of 1419 randomly selected subjects with a minimum age of 20 years, 1107 (78%) took part in the initial examinations. Compared with the whole sample of 1107 participants, the 312 non-responders had the same sex distribution, but were older [54 (SD 18) vs. 48 (SD 17) years; P < 0.001]. From 1991 to 1995, the participants were re-invited. After subjects who had died (n = 83) and those who were severely ill (n = 3) or who had moved (n = 7) were excluded, 1014 persons were left, of whom 823 (81%) again participated. We excluded 113 subjects from the analysis, because their BP (n = 36) or BSe concentration (n = 51) had not been measured, or because urinary volume or creatinine excretion was outside published limits (n = 26).13 Thus, for the present analysis, the study group totalled 710 subjects (50% of those initially selected).

BP measurements
Five trained nurses measured the participants' sitting BP at two home visits 1–3 weeks apart and thereafter at one follow-up visit. After the subjects had rested for 5 min, the nurses measured BP (phase V diastolic) five times consecutively to the nearest 2 mmHg. Standard cuffs had a 12 x 24 cm inflatable portion, but if upper arm girth exceeded 31 cm, larger cuffs with 15 x 35 cm bladders were employed. Every three months, the nurses passed a test requiring them to read BP from a videotape featuring a falling mercury column with Korotkoff sounds (Blood Pressure Measurement, British Medical Association, London, United Kingdom). In view of the cardiovascular risk associated with high-normal BP,14 and the high 4-year progression rates from high-normal BP (130–139/85–89 mmHg) to hypertension (≥140/ ≥ 90 mmHg) in the present population,15 we defined high BP as a BP equal or higher than 130 mmHg systolic or 85 mmHg diastolic, or as a condition requiring antihypertensive medications.16

Other measurements
We used the same questionnaire at baseline and follow-up to collect information on the participants' medical history, intake of medications, and lifestyle including smoking and drinking habits. The questionnaire also provided information on the menstrual cycle of women. Menopause was defined as continuous amenorrhoea from baseline onwards. By use of published tables,17 the energy spent in physical activity was calculated from body weight, the time devoted to sports and work, and the type of physical activity.

At baseline, the participants collected a 24 h urine sample in a wide-neck plastic container for the measurement of sodium, potassium, and creatinine. At baseline, we also measured the BSe concentration in duplicate by graphite furnace atomic absorption spectrometry. We included internal standards in each series of study samples. A series of measurements was repeated whenever duplicate determinations of a sample differed by more than 5% or when the deviation from the internal standard exceeded 10%.

Statistical analysis
For database management and statistical analysis, we used SAS software version 8.1 (SAS Institute Inc., Cary, NC, USA). To study the possible confounding structure in our data set, we assessed in women and men separately the distributions of continuous variables (ANOVA) and the proportions of categorical variables ({chi}2-statistics) across quintiles of the BSe concentration. Our statistical methods also included single and multiple linear regression.

In the cross-sectional analysis, we tested the interaction between gender and BSe for systolic BP and diastolic BP. Because these interaction terms were statistically significant, we analysed women and men separately. In a first regression step, the linear and quadratic terms of age were forced into the models. We considered covariates for the inclusion in the regression models, which are known to be associated with BP, such as age, body mass index, smoking, the 24 h urinary excretion of sodium and potassium, and in women, additionally menopausal status and the use of contraceptive pills at baseline. Furthermore, we applied sensitivity analyses, in which we further adjusted for physical activity and socio-economic class.

Using multiple Cox regression, we modelled time to high BP with the same adjustments as in the cross-sectional analyses while also accounting for the baseline BP. In Cox regression, we additionally tested whether the addition of a squared term of BSe significantly added to the prediction of high BP. We tested possible non-proportionality of survival rates by means of the PROC LIFETEST, as implemented in the SAS package. All P-values refer to two-sided tests.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 Acknowledgements
 References
 
Baseline characteristics of study participants
The distribution of age (48.9 ± 15.2 vs. 48.6 ± 15.3; P = 0.76) and body mass index (26.2 ± 3.6 vs. 26.5 ± 5.8; P = 0.46) was similar in 368 women and 342 men. Smoking and use of alcohol were less frequent in women than in men; 123 women (33.0%) were current smokers and 16 women (4.3%) reported intake of alcohol. Among men, these proportions were 170 (49.1%) and 106 (30.6%), respectively. In smokers, the median tobacco use per day was 16 cigarettes (interquartile range 10–25). In drinkers, the median alcohol consumption was 20 g per day (10–50). A total of 143 women (38.3%) reported natural or surgical menopause, 47 (12.6%) used oral contraceptives, and 3 (0.8%) took hormonal replacement therapy. At baseline, the BSe concentration was lower in men than in women (94.8 ± 19.7 vs. 98.9 ± 18.2; P = 0.0032) and in smokers compared with non-smokers (93.7 vs. 99.1 µg/L; P = 0.0001). Neither in women nor in men, the BSe concentration was significantly associated with age, urinary creatinine, or alcohol intake (Tables 1 and 2).


View this table:
[in this window]
[in a new window]

  		Table 1 Baseline characteristics by quintiles of BSe in women

 

View this table:
[in this window]
[in a new window]

  		Table 2 Baseline characteristics by quintiles of BSe in men

 
Cross-sectional analysis
We noticed significant sex-by-selenium interactions for both systolic BP (P = 0.03) and diastolic BP (P = 0.004). We therefore analysed women and men separately. In men, both before (Figure 1) and after (Table 3) cumulative adjustment for age, body mass index, antihypertensive drug treatment, smoking (0,1), alcohol intake (0,1), and the 24 h urinary excretion of sodium and potassium, systolic BP and diastolic BP at baseline were inversely and independently correlated with the BSe concentration. In men, with adjustments applied as before, systolic BP at follow-up was also inversely correlated with the BSe concentration at baseline (Table 3). Sensitivity analyses with men on antihypertensive treatment excluded or with additional adjustments for socio-economic status and the energy spent in physical activity confirmed these associations. In women, neither before (Figure 1) nor after (Table 3) cumulative adjustment for the aforementioned covariates, as well as menopausal status and contraceptive pill use, BP was not related to BSe.


Figure 4791
View larger version (18K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Figure 1 Cross-sectional unadjusted relation between BP and BSe. Left panels represent women and right panels men.

 

View this table:
[in this window]
[in a new window]

  		Table 3 Differences in BP associated with a 1 SD increase in BSe in the cross-sectional analysis

 
Longitudinal analysis
Follow-up ranged from 3.4 to 8.4 years (median 5.2 years). In women, from baseline to follow-up, systolic BP tended to decrease by 0.53 ± 0.76 (± SE) mmHg (P = 0.60) and diastolic BP increased by 1.72 ± 0.53 mmHg (P = 0.014). In men, the corresponding changes averaged – 2.28 ± 0.76 mmHg (P = 0.03) and 2.00 ± 0.44 mmHg (P = 0.003), respectively. Of 385 subjects with normal BP at baseline, 139 developed high-normal BP or hypertension, of whom 36 (25.8%) started receiving antihypertensive drug treatment. Thus, the overall incidence of high BP was 36 cases per 1000 person-years. In men, the risk of developing high-normal BP or hypertension was inversely and independently associated with BSe (Table 4). A 20 µg/L higher BSe concentration was associated with a 37% (95% CI – 52 to – 17; P = 0.001) lower risk. In women (Table 4), baseline selenium did not predict the incidence of high-normal BP or hypertension; the risk associated with a 20 µg higher BSe was 8% (95% CI – 10 to 27; P = 0.41). To allow for non-linearity, we tested the quadratic term of BSe in multivariate-adjusted Cox models, which already included the linear term of BSe. However, the P-values for the quadratic term did not reach significance in women (P = 0.18) or in men (P = 0.22).


View this table:
[in this window]
[in a new window]

  		Table 4 Hazard ratios for developing high BP

 
Because the lower selenium quintile included the highest number of smokers, we performed a sensitivity analysis with smokers excluded. A 20 µg/L higher BSe in non-smoking men was associated with a 32% (95% CI – 51 to – 2; P = 0.039) lower risk of high-normal BP or hypertension. Further sensitivity analyses revealed that baseline BP, based on the average of the five BP readings taken at the second home visit, and for additional adjustments for socio-economic class, the energy spent in physical activity, or the 24 h urinary creatinine excretion did not materially alter the reported associations. Our prospective results in men also remained consistent when patients on antihypertensive drug treatment during follow-up were excluded [risk reduction per 20 µg/L higher BSe, 46% (95% CI – 37 to – 21; P = 0.001)].


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Acknowledgements
 References
 
The blood concentration of selenium, an antioxidant trace mineral, is suboptimal (<90 µg/L) in an estimated 50% of Western Europeans.2,3 In keeping with these published data,2,3 we found that the 95th percentile of the BSe concentration in our study was 125 µg/L, which is approximately the median of the distribution in the USA.18 The key finding in our study was that in men, but not women, BP was lower by ~2 mmHg systolic and 1 mmHg diastolic for each standard deviation increment in BSe. The risk of men developing high-normal BP or hypertension during 5.2 years of follow-up decreased by 37% for each 1 SD increment in the BSe concentration.

To our knowledge, the present results demonstrate for the first time in a prospective epidemiological context that selenium deficiency might be a risk factor for high BP in men. Virtamo et al.8 did not find a relation between BP and serum selenium. However, this study population of 1100 elderly men was not representative for the whole population. A second cross-sectional study of 722 middle-aged Finnish men demonstrated a negative relation between systolic BP and serum selenium.19 In 1991, Perry et al.6 observed that the intrarenal selenium concentration was 25% lower in hypertensive patients compared with normotensive controls. Rat experiments revealed that administration of sodium selenite via drinking water suppressed the increase in BP in response to infusion of angiotensin II, which has a pro-oxidant activity.20

Selenium is a key component of a number functional selenoproteins required for normal health, including the anti-oxidant glutathione peroxidase enzyme, which prevents oxidation of lipids and phospholipids. In selenium deficiency, a build-up of hydroperoxides inhibits prostacyclin synthetase. This enzyme is responsible for the production of the vasodilatory prostacyclin by the endothelium. Increased oxidative stress stimulates the production of thromboxane, which promotes vasoconstriction and platelet aggregation in vitro21 and in man.22 Adequate selenium intake therefore helps to maintain adequate nitric oxide concentrations23 and to reduce LDL oxidation.24 In selenium-deficient hypercholesterolaemic rats, selenium supplementation enhanced the endothelium-dependent relaxation.25

We observed a relation between BP and BSe in men, but not in women. This was not due to sex differences in the range of values of BP and BSe, or to differential linearity in the BP–selenium association. Gender considerably influences the metabolism of reactive oxygen species.26–28 Indeed, estrogens exert a strong anti-oxidant activity by direct reduction of free radicals and by the stimulation of enzymes, which are crucial for free radical detoxification.27 In experimental studies, female mitochondria compared with male produced significantly less hydrogen peroxide and had higher levels of reduced glutathione, manganese superoxide dismutase, and glutathione peroxidase.28 Thus, the more elaborate anti-oxidative mechanisms in women might explain why we failed to observe any association between BP and BSe. Furthermore, animal and human studies revealed differences in the distribution of selenium across tissues.29 For instance, women compared with men have higher levels of selenium in toenails, whereas their dietary selenium intake is similar.30

Our study should be interpreted within the context of its possible limitations. Observational studies, even if prospective and based on predefined hypotheses, do not prove causality. Indeed, we cannot exclude with certainty that the protective effect of selenium on the development of high-normal BP or hypertension might, owing to other factors, strongly associate with selenium, such as dietary protein intake. On the other hand, our findings are representative for a Western European population. We implemented and maintained a rigorous quality control programme for the measurements of BP and BSe. Nurses visited the participants at home to increase the participation rate and to reduce bias due to attrition in a long-term longitudinal study.

If confirmed, our finding may have important implication for public health. Indeed, a population-wide reduction in systolic pressure by 2 mmHg is likely to result in a 7% decrease in coronary heart disease and a 10% decrease in stroke.31 Such protective effect could be obtained by a mere increase in the average BSe concentration by 20 µg/L. This would require an enrichment of the daily intake of selenium by 13 µg from an estimated 50 µg per day.32,33 At present, soil fortification with selenium is being discussed by the European Union.34 Our study might inform the decision process. Finally, a recent Framingham publication14 also underscored the potential implications of our current findings. It reported that high-normal BP compared with optimal BP (>120/ > 80 mmHg) was associated with a 1.6–2.5-fold increase in the cardiovascular risk.

In conclusion, deficiency of the antioxidant selenium, which is prevalent in Western Europe, might be an underestimated risk factor for the development of high-normal BP or hypertension in men.


   Acknowledgements
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Acknowledgements
References
 
FLEMENGHO is part of the European Project on Genes in Hypertension (EPOGH), which is endorsed by the European Council for Cardiovascular Research and the European Society of Hypertension. The European Union [grants IC15-CT98-0329-EPOGH, QLGI-CT-2000-01137-EURNETGEN, and InGenious HyperCare (LSHM-CT-2006-037093)], the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium (grants G.0424.03 and G.0575.06), and the Katholieke Universiteit Leuven, Belgium (grants OT/99/28, OT/00/25, and OT/05/49) supported research included in this article. J.A.S. is holder of the Pfizer Chair for Hypertension and Cardiovascular Research (http://www.kuleuven.be /mecenaat/leerstoelen/overzicht.htm). FLEMENGHO would not have been possible without the voluntary collaboration of participants and their general practitioners. The municipality Hechtel-Eksel (Belgium) gave logistic support. The authors gratefully acknowledge the expert technical assistance of Sandra Covens, Linda Custers, Marie-Jeanne Jehoul, Katrien Staessen, Hanne Truyens, and Renilde Wolfs (Studies Coordinating Centre, University of Leuven, Belgium).

Conflict of interest: none declared.


   Footnotes
 
In the original online version of this manuscript the number of study participants listed was incorrect. The correct number of participants should have been 368 women and 342 men. The author apologizes that the error was not identified earlier.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Acknowledgements
 References
 

  1. Neve J. (1996) Selenium as a risk factor for cardiovascular diseases. J Cardiovasc Risk 3:42–47.[Medline]
  2. Rayman MP. (1997) Dietary selenium: time to act. BMJ 314:387–388.[Free Full Text]
  3. Rayman MP. (2000) The importance of selenium to human health. Lancet 356:233–241.[CrossRef][Web of Science][Medline]
  4. Salonen JT, Alfthan G, Huttunen JK, Pikkarainen J, Puska P. (1982) Association between cardiovascular death and myocardial-infarction and serum selenium in a matched-pair longitudinal study. Lancet 2:175–179.[Web of Science][Medline]
  5. Oster O and Prellwitz W. (1989) The daily dietary selenium intake of West German adults. Biol Trace Elem Res 20:1–14.[Medline]
  6. Perry H, Masironi R, Parr R, Miller J. (1991) Concentration of trace metals (Cd, Zn, Se, Cu, Cr, and Fe) in organs (heart, kidney, and liver) of subjects with myocardial infarction or hypertension: WHO/IAEA myocardial infarction and hypertension autopsy study. J Trace Elem Exp Med 4:109–128.
  7. Salonen JT, Happonen P, Seppanen K, Rauramaa R. (1987) Association of alcohol-consumption with plasma-lipoproteins, blood-pressure and catecholamine excretion. Circulation 76:532.
  8. Virtamo J, Valkeila E, Alfthan G, Punsar S, Huttunen JK, Karvonen MJ. (1985) Serum selenium and the risk of coronary heart-disease and stroke. Am J Epidemiol 122:276–282.[Abstract/Free Full Text]
  9. Jeserich M, Schindler T, Olschewski M, Unmussig M, Just H, Solzbach U. (1999) Vitamin C improves endothelial function of epicardial coronary arteries in patients with hypercholesterolaemia or essential hypertension—assessed by cold pressor testing. Eur Heart J 20:1676–1680.[Abstract/Free Full Text]
  10. Redon J, Oliva MR, Tormos C, Giner V, Chaves J, Iradi A, Saez GT. (2003) Antioxidant activities and oxidative stress byproducts in human hypertension. Hypertension 41:1096–1101.[Abstract/Free Full Text]
  11. Katayama Y, Shige H, Yamamoto A, Hirata F, Yasuda H. (2004) Oral vitamin C ameliorates smoking-induced arterial wall stiffness in healthy volunteers. J Atheroscler Thromb 11:354–357.[Medline]
  12. Staessen JA, Wang JG, Brand E, Barlassina C, Birkenhäger WH, Herrmann SM, Fagard R, Tizzoni L, Bianchi G. (2001) Effects of three candidate genes on prevalence and incidence of hypertension in a Caucasian population. J Hypertens 19:1349–1358.[CrossRef][Web of Science][Medline]
  13. Staessen J, Bulpitt C, Fagard R, Joossens JV, Lijnen P, Amery A. (1983) Four urinary cations and blood pressure: a population study in two Belgian towns. Am J Epidemiol 117:676–687.[Abstract/Free Full Text]
  14. Vasan RS, Larson MG, Leip EP, Evans JC, O'Donnell CJ, Kannel WB, Levy D. (2001) Impact of high-normal blood pressure on the risk of cardiovascular disease. N Engl J Med 345:1291–1297.[Abstract/Free Full Text]
  15. Zhang H, Thijs L, Kuznetsova T, Fagard RH, Li X, Staessen JA. (2006) Progression of hypertension in the non-hypertensive participants in the Flemish Study on Environment, Genes and Health Outcomes. J Hypertens 24:1719–1727.[Web of Science][Medline]
  16. . European Society of Hypertension/European Society of Cardiology Guidelines Committee. (2003) 2003 European Society of Hypertension/European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 21:1011–1053.[CrossRef][Web of Science][Medline]
  17. McArdle WD, Katch FI, Katch VL. (1991) Exercise Physiology: Energy, Nutrition, and Human Performance(Lea and Febiger, Philadelphia) pp. p804–811.
  18. Niskar AS, Paschal DC, Kieszak SM, Flegal KM, Bowman B, Gunter EW, Pirkle JL, Rubin C, Sampson EJ, McGeehin M. (2003) Serum selenium levels in the US population: Third National Health and Nutrition Examination Survey, 1988–1994. Biol Trace Elem Res 91:1–10.[CrossRef][Web of Science][Medline]
  19. Salonen JT, Salonen R, Seppanen K, Kantola M, Parviainen M, Alfthan G, Maenpaa PH, Taskinen E, Rauramaa R. (1988) Relationship of serum selenium and antioxidants to plasma lipoproteins, platelet aggregability and prevalent ischaemic heart disease in Eastern Finnish men. Atherosclerosis 70:155–160.[CrossRef][Web of Science][Medline]
  20. Hilse H, Oehme P, Krause W, Hecht K. (1979) Effect of sodium selenite on experimental hypertension in rat. Acta Physiol Pharmacol Bulg 5:47–50.[Medline]
  21. Weaver JA, Maddox JF, Cao YZ, Mullarky IK, Sordillo LM. (2001) Increased 15-HPETE production decreases prostacyclin synthase activity during oxidant stress in aortic endothelial cells. Free Radic Biol Med 30:299–308.[CrossRef][Web of Science][Medline]
  22. Davi G, Guagnano MT, Ciabattoni G, Basili S, Falco A, Marinopiccoli M, Nutini M, Sensi S, Patrono C. (2002) Platelet activation in obese women: role of inflammation and oxidant stress. JAMA 288:2008–2014.[Abstract/Free Full Text]
  23. McCarty MF. (1999) Oxidants downstream from superoxide inhibit nitric oxide production by vascular endothelium—a key role for selenium-dependent enzymes in vascular health. Med Hypotheses 53:315–325.[CrossRef][Web of Science][Medline]
  24. Rosenblat M and Aviram M. (1998) Macrophage glutathione content and glutathione peroxidase activity are inversely related to cell-mediated oxidation of LDL: in vitro and in vivo studies. Free Radic Biol Med 24:305–317.[CrossRef][Web of Science][Medline]
  25. Raij L, Nagy J, Coffee K, DeMaster EG. (1993) Hypercholesterolemia promotes endothelial dysfunction in vitamin E- and selenium-deficient rats. Hypertension 22:56–61.[Abstract/Free Full Text]
  26. Lacy F, Kailasam MT, O'Connor DT, Schmid-Schonbein GW, Parmer RJ. (2000) Plasma hydrogen peroxide production in human essential hypertension—role of heredity, gender, and ethnicity. Hypertension 36:878–884.[Abstract/Free Full Text]
  27. Rosano GM, Chierchia SL, Leonardo F, Beale CM, Collins P. (1996) Cardioprotective effects of ovarian hormones. Eur Heart J 17:Suppl. D, 15–19.
  28. Vina J, Sastre J, Pallardo F, Borras C. (2003) Mitochondrial theory of ageing: importance to explain why females live longer than males. Antioxid Redox Signal 5:549–556.[CrossRef][Web of Science][Medline]
  29. Waters DJ, Chiang EC, Cooley DM, Morris JS. (2004) Making sense of sex and supplements: differences in the anticarcinogenic effects of selenium in men and women. Mutat Res 551:91–107.[Web of Science][Medline]
  30. van den Brandt PA, Goldbohm RA, van't Veer P, Bode P, Hermus RJ, Sturmans F. (1993) Predictors of toenail selenium levels in men and women. Cancer Epidemiol Biomarkers Prev 2:107–112.[Abstract]
  31. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. (2002) Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 360:1903–1913.[CrossRef][Web of Science][Medline]
  32. Neve J, Vertongen F, Peretz A, Carpentier YA. (1989) Usual values of selenium and glutathione peroxidase in a Belgian population. Ann Biol Clin 47:138–143.[Medline]
  33. Neve J. (1995) Human selenium supplementation as assessed by changes in blood selenium concentration and glutathione peroxidase activity. J Trace Elem Med Biol 9:65–73.[Web of Science][Medline]
  34. Arthur JR. (2003) Selenium supplementation: does soil supplementation help and why? Proc Nutr Soc 62:393–397.[CrossRef][Web of Science][Medline]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 HypertensionHome page
B. Valera, E. Dewailly, and P. Poirier
Environmental Mercury Exposure and Blood Pressure Among Nunavik Inuit Adults
Hypertension, November 1, 2009; 54(5): 981 - 986.
[Abstract] [Full Text] [PDF]

Home page
 Circ Cardiovasc Qual OutcomesHome page
M. Laclaustra, A. Navas-Acien, S. Stranges, J. M. Ordovas, and E. Guallar
Serum Selenium Concentrations and Hypertension in the US Population
Circ Cardiovasc Qual Outcomes, July 1, 2009; 2(4): 369 - 376.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
W. C. Hawkes and L. J. Laslett
Selenium supplementation does not improve vascular responsiveness in healthy North American men
Am J Physiol Heart Circ Physiol, February 1, 2009; 296(2): H256 - H262.
[Abstract] [Full Text] [PDF]

Home page
 Nutr Clin PractHome page
M. G. Boosalis
The Role of Selenium in Chronic Disease
Nutr Clin Pract, April 1, 2008; 23(2): 152 - 160.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
L. Schomburg
Selene, the goddess of the moon: does she shine on men only?
Eur. Heart J., August 2, 2007; 28(16): 2043 - 2044.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
28/5/628    most recent
ehl479v2
ehl479v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Nawrot, T. S.
Right arrow Articles by Struijker-Boudier, H. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nawrot, T. S.
Right arrow Articles by Struijker-Boudier, H. A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?