Skip to main content
Top
Published in: BMC Cardiovascular Disorders 1/2015

Open Access 01-12-2015 | Research article

Circulating concentrations of endothelin-1 predict coronary heart disease in women but not in men: a longitudinal observational study in the Vara-Skövde Cohort

Authors: Bledar Daka, Josefin Olausson, Charlotte A. Larsson, Margareta I. Hellgren, Lennart Råstam, Per-Anders Jansson, Ulf Lindblad

Published in: BMC Cardiovascular Disorders | Issue 1/2015

Login to get access

Abstract

Background

The vasoconstricting peptide endothelin-1 has been proposed to be a marker of cardiovascular disease. Our aim was to investigate whether circulating endothelin-1 levels predict coronary heart disease (CHD) in Sweden.

Methods

In 2002–2005, 2816 adult participants (30–74 years) were randomly selected from two municipalities in south-western Sweden. Cardiovascular risk factors and endothelin-1 levels were assessed at baseline, and incident CHD was followed-up in all participants through 2011. After exclusion of 50 participants due to known CHD at baseline and 21 participants because of unsuccessful analysis of endothelin-1, 2745 participants were included in the study. In total, 72 CHD events (52 in men and 20 in women) were registered during the follow-up time.

Results

We showed that baseline circulating endothelin-1 levels were higher in women with incident CHD than in women without CHD (3.2 pg/ml, SE: 0.36 vs 2.4 pg/ml, SE: 0.03, p = 0.003) whereas this difference was not observed in men (2.3 pg/ml, SE: 0.16 vs 2.3 pg/ml, SE: 0.04, p = 0.828). An age-adjusted Cox proportional regression analysis showed an enhanced risk of CHD with increasing baseline endothelin-1 levels in women (hazard ratio (HR) = 1.51, 95 % CI = 1.1–2.1, p = 0.015) but not in men (HR = 0.98, 95 % CI = 0.8–1.2, p = 0.854). Furthermore, the predictive value of endothelin-1 for incident CHD in women was still significant after adjustments for age, HOMA-IR, apolipoprotein (apo)B/apoA1 and smoking (HR = 1.53, CI = 1.1–1.2, p = 0.024).

Conclusion

Circulating endothelin-1 levels may predict CHD in women.
Literature
1.
go back to reference Faxon DP, Creager MA, Smith Jr SC, Pasternak RC, Olin JW, Bettmann MA, et al. Atherosclerotic Vascular Disease Conference: Executive summary: Atherosclerotic Vascular Disease Conference proceeding for healthcare professionals from a special writing group of the American Heart Association. Circulation. 2004;109:2595–604.CrossRefPubMed Faxon DP, Creager MA, Smith Jr SC, Pasternak RC, Olin JW, Bettmann MA, et al. Atherosclerotic Vascular Disease Conference: Executive summary: Atherosclerotic Vascular Disease Conference proceeding for healthcare professionals from a special writing group of the American Heart Association. Circulation. 2004;109:2595–604.CrossRefPubMed
2.
go back to reference Nichols M, Townsend N, Scarborough P, Rayner M. Cardiovascular disease in Europe 2014: epidemiological update. Eur Heart J. 2014;35(42):2929.CrossRefPubMed Nichols M, Townsend N, Scarborough P, Rayner M. Cardiovascular disease in Europe 2014: epidemiological update. Eur Heart J. 2014;35(42):2929.CrossRefPubMed
3.
go back to reference Bonetti PO, Lerman LO, Lerman A. Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol. 2003;23:168–75.CrossRefPubMed Bonetti PO, Lerman LO, Lerman A. Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol. 2003;23:168–75.CrossRefPubMed
4.
go back to reference Moreau P. Endothelin in hypertension: a role for receptor antagonists? Cardiovasc Res. 1998;39:534–42.CrossRefPubMed Moreau P. Endothelin in hypertension: a role for receptor antagonists? Cardiovasc Res. 1998;39:534–42.CrossRefPubMed
5.
go back to reference Zeiher AM, Goebel H, Schachinger V, Ihling C. Tissue endothelin-1 immunoreactivity in the active coronary atherosclerotic plaque. A clue to the mechanism of increased vasoreactivity of the culprit lesion in unstable angina. Circulation. 1995;91:941–7.CrossRefPubMed Zeiher AM, Goebel H, Schachinger V, Ihling C. Tissue endothelin-1 immunoreactivity in the active coronary atherosclerotic plaque. A clue to the mechanism of increased vasoreactivity of the culprit lesion in unstable angina. Circulation. 1995;91:941–7.CrossRefPubMed
6.
go back to reference Zouridakis EG, Schwartzman R, Garcia-Moll X, Cox ID, Fredericks S, Holt DW, et al. Increased plasma endothelin levels in angina patients with rapid coronary artery disease progression. Eur Heart J. 2001;22:1578–84.CrossRefPubMed Zouridakis EG, Schwartzman R, Garcia-Moll X, Cox ID, Fredericks S, Holt DW, et al. Increased plasma endothelin levels in angina patients with rapid coronary artery disease progression. Eur Heart J. 2001;22:1578–84.CrossRefPubMed
7.
go back to reference Kanaya AM, Barrett-Connor E, Wassel Fyr CL. Endothelin-1 and prevalent coronary heart disease in older men and women (the Rancho Bernardo Study). Am J Cardiol. 2007;99:486–90.PubMedCentralCrossRefPubMed Kanaya AM, Barrett-Connor E, Wassel Fyr CL. Endothelin-1 and prevalent coronary heart disease in older men and women (the Rancho Bernardo Study). Am J Cardiol. 2007;99:486–90.PubMedCentralCrossRefPubMed
8.
go back to reference Ruo B, Tripputi MT, Hsue PY, Saigo M, Ouyang P, Waters DD. Usefulness of serum endothelin levels in predicting death and myocardial infarction but not coronary progression in postmenopausal women with coronary disease (from the Women’s Angiographic Vitamin and Estrogen [WAVE] study). Am J Cardiol. 2005;96:335–8.CrossRefPubMed Ruo B, Tripputi MT, Hsue PY, Saigo M, Ouyang P, Waters DD. Usefulness of serum endothelin levels in predicting death and myocardial infarction but not coronary progression in postmenopausal women with coronary disease (from the Women’s Angiographic Vitamin and Estrogen [WAVE] study). Am J Cardiol. 2005;96:335–8.CrossRefPubMed
9.
go back to reference Novo G, Sansone A, Rizzo M, Guarneri FP, Pernice C, Novo S. High plasma levels of endothelin-1 enhance the predictive value of preclinical atherosclerosis for future cerebrovascular and cardiovascular events: a 20-year prospective study. J Cardiovasc Med (Hagerstown). 2014;15:696–701.CrossRef Novo G, Sansone A, Rizzo M, Guarneri FP, Pernice C, Novo S. High plasma levels of endothelin-1 enhance the predictive value of preclinical atherosclerosis for future cerebrovascular and cardiovascular events: a 20-year prospective study. J Cardiovasc Med (Hagerstown). 2014;15:696–701.CrossRef
10.
go back to reference Larsson CA, Daka B, Gullberg B, Rastam L, Lindblad U. Clusters of AMI risk factors and their association with left ventricular hypertrophy: a population-based study within the Skaraborg Project, Sweden. Int J Cardiol. 2013;168:5416–21.CrossRefPubMed Larsson CA, Daka B, Gullberg B, Rastam L, Lindblad U. Clusters of AMI risk factors and their association with left ventricular hypertrophy: a population-based study within the Skaraborg Project, Sweden. Int J Cardiol. 2013;168:5416–21.CrossRefPubMed
11.
go back to reference Hellgren MI, Daka B, Jansson PA, Lindblad U, Larsson CA. Insulin resistance predicts early cardiovascular morbidity in men without diabetes mellitus, with effect modification by physical activity. Eur J Prev Cardiol. 2015;22(7):940–9.CrossRefPubMed Hellgren MI, Daka B, Jansson PA, Lindblad U, Larsson CA. Insulin resistance predicts early cardiovascular morbidity in men without diabetes mellitus, with effect modification by physical activity. Eur J Prev Cardiol. 2015;22(7):940–9.CrossRefPubMed
12.
go back to reference Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42:1206-52. [PubMed]. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42:1206-52. [PubMed].
13.
go back to reference Haffner SM, Miettinen H, Stern MP. The homeostasis model in the San Antonio Heart Study. Diabetes Care. 1997;20:1087–92.CrossRefPubMed Haffner SM, Miettinen H, Stern MP. The homeostasis model in the San Antonio Heart Study. Diabetes Care. 1997;20:1087–92.CrossRefPubMed
14.
go back to reference Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998;15:539–53.CrossRefPubMed Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998;15:539–53.CrossRefPubMed
15.
go back to reference Andersen L, Dinesen B, Jorgensen PN, Poulsen F, Roder ME. Enzyme immunoassay for intact human insulin in serum or plasma. Clin Chem. 1993;39:578–82.PubMed Andersen L, Dinesen B, Jorgensen PN, Poulsen F, Roder ME. Enzyme immunoassay for intact human insulin in serum or plasma. Clin Chem. 1993;39:578–82.PubMed
16.
go back to reference Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999;84:3666–72.CrossRefPubMed Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999;84:3666–72.CrossRefPubMed
17.
go back to reference Rinaldi S, Geay A, Dechaud H, Biessy C, Zeleniuch-Jacquotte A, Akhmedkhanov A, et al. Validity of free testosterone and free estradiol determinations in serum samples from postmenopausal women by theoretical calculations. Cancer Epidemiol Biomarkers Prev. 2002;11:1065–71.PubMed Rinaldi S, Geay A, Dechaud H, Biessy C, Zeleniuch-Jacquotte A, Akhmedkhanov A, et al. Validity of free testosterone and free estradiol determinations in serum samples from postmenopausal women by theoretical calculations. Cancer Epidemiol Biomarkers Prev. 2002;11:1065–71.PubMed
18.
go back to reference Merlo J, Lindblad U, Pessah-Rasmussen H, Hedblad B, Rastam J, Isacsson SO, et al. Comparison of different procedures to identify probable cases of myocardial infarction and stroke in two Swedish prospective cohort studies using local and national routine registers. Eur J Epidemiol. 2000;16:235–43.CrossRefPubMed Merlo J, Lindblad U, Pessah-Rasmussen H, Hedblad B, Rastam J, Isacsson SO, et al. Comparison of different procedures to identify probable cases of myocardial infarction and stroke in two Swedish prospective cohort studies using local and national routine registers. Eur J Epidemiol. 2000;16:235–43.CrossRefPubMed
19.
go back to reference Lindblad U, Rastam L, Ranstam J, Peterson M. Validity of register data on acute myocardial infarction and acute stroke: the Skaraborg Hypertension Project. Scand J Soc Med. 1993;21:3–9.PubMed Lindblad U, Rastam L, Ranstam J, Peterson M. Validity of register data on acute myocardial infarction and acute stroke: the Skaraborg Hypertension Project. Scand J Soc Med. 1993;21:3–9.PubMed
20.
go back to reference Melander O, Newton-Cheh C, Almgren P, Hedblad B, Berglund G, Engstrom G, et al. Novel and conventional biomarkers for prediction of incident cardiovascular events in the community. JAMA. 2009;302:49–57.PubMedCentralCrossRefPubMed Melander O, Newton-Cheh C, Almgren P, Hedblad B, Berglund G, Engstrom G, et al. Novel and conventional biomarkers for prediction of incident cardiovascular events in the community. JAMA. 2009;302:49–57.PubMedCentralCrossRefPubMed
21.
go back to reference Polderman KH, Stehouwer CD, van Kamp GJ, Dekker GA, Verheugt FW, Gooren LJ. Influence of sex hormones on plasma endothelin levels. Ann Intern Med. 1993;118:429–32.CrossRefPubMed Polderman KH, Stehouwer CD, van Kamp GJ, Dekker GA, Verheugt FW, Gooren LJ. Influence of sex hormones on plasma endothelin levels. Ann Intern Med. 1993;118:429–32.CrossRefPubMed
22.
go back to reference Morey AK, Razandi M, Pedram A, Hu RM, Prins BA, Levin ER. Oestrogen and progesterone inhibit the stimulated production of endothelin-1. Biochem J. 1998;330(Pt 3):1097–105.PubMedCentralCrossRefPubMed Morey AK, Razandi M, Pedram A, Hu RM, Prins BA, Levin ER. Oestrogen and progesterone inhibit the stimulated production of endothelin-1. Biochem J. 1998;330(Pt 3):1097–105.PubMedCentralCrossRefPubMed
23.
go back to reference Lin CL, Dumont AS, Wu SC, Wang CJ, Howng SL, Huang YF, et al. 17beta-estradiol inhibits endothelin-1 production and attenuates cerebral vasospasm after experimental subarachnoid hemorrhage. Exp Biol Med (Maywood). 2006;231:1054–7. Lin CL, Dumont AS, Wu SC, Wang CJ, Howng SL, Huang YF, et al. 17beta-estradiol inhibits endothelin-1 production and attenuates cerebral vasospasm after experimental subarachnoid hemorrhage. Exp Biol Med (Maywood). 2006;231:1054–7.
24.
go back to reference Ding D, Starke RM, Dumont AS, Owens GK, Hasan DM, Chalouhi N, et al. Therapeutic implications of estrogen for cerebral vasospasm and delayed cerebral ischemia induced by aneurysmal subarachnoid hemorrhage. Biomed Res Int. 2014;2014:727428.PubMedCentralPubMed Ding D, Starke RM, Dumont AS, Owens GK, Hasan DM, Chalouhi N, et al. Therapeutic implications of estrogen for cerebral vasospasm and delayed cerebral ischemia induced by aneurysmal subarachnoid hemorrhage. Biomed Res Int. 2014;2014:727428.PubMedCentralPubMed
25.
go back to reference Caballero AE, Arora S, Saouaf R, Lim SC, Smakowski P, Park JY, et al. Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes. Diabetes. 1999;48:1856–62.CrossRefPubMed Caballero AE, Arora S, Saouaf R, Lim SC, Smakowski P, Park JY, et al. Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes. Diabetes. 1999;48:1856–62.CrossRefPubMed
26.
go back to reference Maeda S, Tanabe T, Miyauchi T, Otsuki T, Sugawara J, Iemitsu M, et al. Aerobic exercise training reduces plasma endothelin-1 concentration in older women. J Appl Physiol (1985). 2003;95:336–41.CrossRef Maeda S, Tanabe T, Miyauchi T, Otsuki T, Sugawara J, Iemitsu M, et al. Aerobic exercise training reduces plasma endothelin-1 concentration in older women. J Appl Physiol (1985). 2003;95:336–41.CrossRef
27.
go back to reference Schiffrin EL. State-of-the-Art lecture. Role of endothelin-1 in hypertension. Hypertension. 1999;34:876–81.CrossRefPubMed Schiffrin EL. State-of-the-Art lecture. Role of endothelin-1 in hypertension. Hypertension. 1999;34:876–81.CrossRefPubMed
28.
go back to reference Shichiri M, Hirata Y, Ando K, Emori T, Ohta K, Kimoto S, et al. Plasma endothelin levels in hypertension and chronic renal failure. Hypertension. 1990;15:493–6.CrossRefPubMed Shichiri M, Hirata Y, Ando K, Emori T, Ohta K, Kimoto S, et al. Plasma endothelin levels in hypertension and chronic renal failure. Hypertension. 1990;15:493–6.CrossRefPubMed
29.
go back to reference Schneider MP, Boesen EI, Pollock DM. Contrasting actions of endothelin ET(A) and ET(B) receptors in cardiovascular disease. Annu Rev Pharmacol Toxicol. 2007;47:731–59.PubMedCentralCrossRefPubMed Schneider MP, Boesen EI, Pollock DM. Contrasting actions of endothelin ET(A) and ET(B) receptors in cardiovascular disease. Annu Rev Pharmacol Toxicol. 2007;47:731–59.PubMedCentralCrossRefPubMed
30.
go back to reference Hiatt WR, Stoll S, Nies AS. Effect of beta-adrenergic blockers on the peripheral circulation in patients with peripheral vascular disease. Circulation. 1985;72:1226–31.CrossRefPubMed Hiatt WR, Stoll S, Nies AS. Effect of beta-adrenergic blockers on the peripheral circulation in patients with peripheral vascular disease. Circulation. 1985;72:1226–31.CrossRefPubMed
31.
go back to reference Ingram DM, House AK, Thompson GH, Stacey MC, Castleden WM, Lovegrove FT. Beta-adrenergic blockade and peripheral vascular disease. Med J Aust. 1982;1:509–11.PubMed Ingram DM, House AK, Thompson GH, Stacey MC, Castleden WM, Lovegrove FT. Beta-adrenergic blockade and peripheral vascular disease. Med J Aust. 1982;1:509–11.PubMed
32.
go back to reference Wedel H, Demets D, Deedwania P, Fagerberg B, Goldstein S, Gottlieb S, et al. Challenges of subgroup analyses in multinational clinical trials: experiences from the MERIT-HF trial. Am Heart J. 2001;142:502–11.CrossRefPubMed Wedel H, Demets D, Deedwania P, Fagerberg B, Goldstein S, Gottlieb S, et al. Challenges of subgroup analyses in multinational clinical trials: experiences from the MERIT-HF trial. Am Heart J. 2001;142:502–11.CrossRefPubMed
Metadata
Title
Circulating concentrations of endothelin-1 predict coronary heart disease in women but not in men: a longitudinal observational study in the Vara-Skövde Cohort
Authors
Bledar Daka
Josefin Olausson
Charlotte A. Larsson
Margareta I. Hellgren
Lennart Råstam
Per-Anders Jansson
Ulf Lindblad
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2015
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-015-0141-y

Other articles of this Issue 1/2015

BMC Cardiovascular Disorders 1/2015 Go to the issue