Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Cardiovascular biomarkers and sex: the case for women

Nature Reviews Cardiology volume 12, pages 588–596 (2015)Cite this article

Subjects

Key Points

  • Cardiac troponin level is prognostic for adverse cardiovascular outcomes in both sexes

  • Increasingly sensitive assays for cardiac troponins will renew focus on sex-specific differences in troponin concentrations, and might increase the relevance of sex-specific cut-off points for diagnosis, prognosis, and risk prediction

  • Healthy women have a higher natriuretic peptide level than healthy men, but the same cut-off points for diagnosis and prognosis of heart failure can generally be used in both sexes

  • Soluble ST2 level is lower in healthy women than healthy men; however; a cut-off point of 35 ng/ml seems to be robust for prognosis in both sexes with heart failure

  • Proneurotensin might improve prediction of incident cardiovascular disease, diabetes mellitus, and breast cancer in women, although further studies are needed to confirm these associations

Abstract

Measurement of biomarkers is a critical component of cardiovascular care. Women and men differ in their cardiac physiology and manifestations of cardiovascular disease. Although most cardiovascular biomarkers are used by clinicians without taking sex into account, sex-specific differences in biomarkers clearly exist. Baseline concentrations of many biomarkers (including cardiac troponin, natriuretic peptides, galectin-3, and soluble ST2) differ in men versus women, but these sex-specific differences do not generally translate into a need for differential sex-based cut-off points. Furthermore, most biomarkers are similarly diagnostic and prognostic, regardless of sex. Two potential exceptions are cardiac troponins measured by high-sensitivity assay, and proneurotensin. Troponin levels are lower in women than in men and, with the use of high-sensitivity assays, sex-specific cut-off points might improve the diagnosis of myocardial infarction. Proneurotensin is a novel biomarker that was found to be predictive of incident cardiovascular disease in women, but not men, and was also predictive of incident breast cancer. If confirmed, proneurotensin might be a unique biomarker of disease risk in women. With any biomarker, an understanding of sex-specific differences might improve its use and might also lead to an enhanced understanding of the physiological differences between the hearts of men and women.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Outcome of patients in the TACTICS-TIMI 18 trial by biomarker status and treatment strategy.
Figure 2: Overview of the biological actions and clinical associations of proneurotensin.
Figure 3: Proneurotensin tertile and incident disease in women in the Malmö Diet and Cancer Study.89

Similar content being viewed by others

References

  1. Mozaffarian, D. et al. Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation 131, e29–e322 (2015).

    PubMed  Google Scholar 

  2. WHO. The top 10 causes of death. The 10 leading causes of death in the world, 2000 and 2012 [online], (2014).

  3. Diercks, D. B. et al. Risk stratification in women enrolled in the Acute Decompensated Heart Failure National Registry Emergency Module (ADHERE-EM). Acad. Emerg. Med. 15, 151–158 (2008).

    Article  PubMed  Google Scholar 

  4. Meyer, S. et al. Neurohormonal and clinical sex differences in heart failure. Eur. Heart J. 34, 2538–2547 (2013).

    Article  CAS  PubMed  Google Scholar 

  5. Meyer, S. et al. Sex-specific acute heart failure phenotypes and outcomes from PROTECT. Eur. J. Heart Fail. 15, 1374–1381 (2013).

    Article  PubMed  Google Scholar 

  6. Apple, F. S., Quist, H. E., Doyle, P. J., Otto, A. P. & Murakami, M. M. Plasma 99th percentile reference limits for cardiac troponin and creatine kinase MB mass for use with European Society of Cardiology/American College of Cardiology consensus recommendations. Clin. Chem. 49, 1331–1336 (2003).

    Article  CAS  PubMed  Google Scholar 

  7. Apple, F. S., Ler, R. & Murakami, M. M. Determination of 19 cardiac troponin I and T assay 99th percentile values from a common presumably healthy population. Clin. Chem. 58, 1574–1581 (2012).

    Article  CAS  PubMed  Google Scholar 

  8. Giannitsis, E. et al. Analytical validation of a high-sensitivity cardiac troponin T assay. Clin. Chem. 56, 254–261 (2010).

    Article  CAS  PubMed  Google Scholar 

  9. Gore, M. O. et al. Age- and sex-dependent upper reference limits for the high-sensitivity cardiac troponin T assay. J. Am. Coll. Cardiol. 63, 1441–1448 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Omland, T. et al. A sensitive cardiac troponin T assay in stable coronary artery disease. N. Engl. J. Med. 361, 2538–2547 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Laufer, E. M. et al. The extent of coronary atherosclerosis is associated with increasing circulating levels of high sensitive cardiac troponin T. Arterioscler. Thromb. Vasc. Biol. 30, 1269–1275 (2010).

    Article  CAS  PubMed  Google Scholar 

  12. Pope, J. H. et al. Missed diagnoses of acute cardiac ischemia in the emergency department. N. Engl. J. Med. 342, 1163–1170 (2000).

    Article  CAS  PubMed  Google Scholar 

  13. Bairey Merz, C. N. et al. Insights from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) study. Part II: gender differences in presentation, diagnosis, and outcome with regard to gender-based pathophysiology of atherosclerosis and macrovascular and microvascular coronary disease. J. Am. Coll. Cardiol. 47 (Suppl. 1), 21S–29S (2006).

    Article  Google Scholar 

  14. Thygesen, K. et al. Third universal definition of myocardial infarction. Nat. Rev. Cardiol. 9, 620–633 (2012).

    Article  PubMed  Google Scholar 

  15. Bohula May, E. A. et al. Prognostic performance of a high-sensitivity cardiac troponin I assay in patients with non-ST-elevation acute coronary syndrome. Clin. Chem. 60, 158–164 (2014).

    Article  CAS  PubMed  Google Scholar 

  16. Shah, A. S. et al. High sensitivity cardiac troponin and the under-diagnosis of myocardial infarction in women: prospective cohort study. BMJ 350, g7873 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Wiviott, S. D. et al. Differential expression of cardiac biomarkers by gender in patients with unstable angina/non-ST-elevation myocardial infarction: a TACTICS-TIMI 18 (Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction 18) substudy. Circulation 109, 580–586 (2004).

    Article  CAS  PubMed  Google Scholar 

  18. Balmelli, C. et al. Comparison of the performances of cardiac troponins, including sensitive assays, and copeptin in the diagnostic of acute myocardial infarction and long-term prognosis between women and men. Am. Heart J. 166, 30–37 (2013).

    Article  CAS  PubMed  Google Scholar 

  19. O'Donoghue, M. et al. Early invasive vs conservative treatment strategies in women and men with unstable angina and non-ST-segment elevation myocardial infarction: a meta-analysis. JAMA 300, 71–80 (2008).

    Article  CAS  PubMed  Google Scholar 

  20. de Lemos, J. A. et al. Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA 304, 2503–2512 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Saunders, J. T. et al. Cardiac troponin T measured by a highly sensitive assay predicts coronary heart disease, heart failure, and mortality in the Atherosclerosis Risk in Communities Study. Circulation 123, 1367–1376 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. deFilippi, C. R. et al. Association of serial measures of cardiac troponin T using a sensitive assay with incident heart failure and cardiovascular mortality in older adults. JAMA 304, 2494–2502 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. McKie, P. M. et al. High-sensitivity troponin I and amino-terminal pro-B-type natriuretic peptide predict heart failure and mortality in the general population. Clin. Chem. 60, 1225–1233 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Zeller, T. et al. High population prevalence of cardiac troponin I measured by a high-sensitivity assay and cardiovascular risk estimation: the MORGAM Biomarker Project Scottish Cohort. Eur. Heart J. 35, 271–281 (2014).

    Article  CAS  PubMed  Google Scholar 

  25. Nambi, V. et al. Troponin T and N-terminal pro-B-type natriuretic peptide: a biomarker approach to predict heart failure risk—the Atherosclerosis Risk in Communities Study. Clin. Chem. 59, 1802–1810 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Dallmeier, D. et al. Sex-specific associations of established and emerging cardiac biomarkers with all-cause mortality in older adults: the ActiFE study. Clin. Chem. 61, 389–399 (2015).

    Article  CAS  PubMed  Google Scholar 

  27. Masson, S. et al. High-sensitivity cardiac troponin T for detection of subtle abnormalities of cardiac phenotype in a general population of elderly individuals. J. Intern. Med. 273, 306–317 (2013).

    Article  CAS  PubMed  Google Scholar 

  28. Eggers, K. M., Venge, P., Lindahl, B. & Lind, L. Cardiac troponin I levels measured with a high-sensitive assay increase over time and are strong predictors of mortality in an elderly population. J. Am. Coll. Cardiol. 61, 1906–1913 (2013).

    Article  CAS  PubMed  Google Scholar 

  29. Glick, D., DeFilippi, C. R., Christenson, R., Gottdiener, J. S. & Seliger, S. L. Long-term trajectory of two unique cardiac biomarkers and subsequent left ventricular structural pathology and risk of incident heart failure in community-dwelling older adults at low baseline risk. JACC Heart Fail. 1, 353–360 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Daniels, L. B. & Maisel, A. S. Natriuretic peptides. J. Am. Coll. Cardiol. 50, 2357–2368 (2007).

    Article  CAS  PubMed  Google Scholar 

  31. Raymond, I. et al. The influence of age, sex and other variables on the plasma level of N-terminal pro brain natriuretic peptide in a large sample of the general population. Heart 89, 745–751 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Redfield, M. M. et al. Plasma brain natriuretic peptide concentration: impact of age and gender. J. Am. Coll. Cardiol. 40, 976–982 (2002).

    Article  CAS  PubMed  Google Scholar 

  33. Wang, T. J. et al. Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N. Engl. J. Med. 350, 655–663 (2004).

    Article  CAS  PubMed  Google Scholar 

  34. Wang, T. J. et al. Impact of age and sex on plasma natriuretic peptide levels in healthy adults. Am. J. Cardiol. 90, 254–258 (2002).

    Article  CAS  PubMed  Google Scholar 

  35. Luchner, A. et al. Long-term pattern of brain natriuretic peptide and N-terminal pro brain natriuretic peptide and its determinants in the general population: contribution of age, gender, and cardiac and extra-cardiac factors. Eur. J. Heart Fail. 15, 859–867 (2013).

    Article  CAS  PubMed  Google Scholar 

  36. Daniels, L. B. et al. Influence of age, race, sex, and body mass index on interpretation of midregional pro atrial natriuretic peptide for the diagnosis of acute heart failure: results from the BACH multinational study. Eur. J. Heart Fail. 14, 22–31 (2012).

    Article  CAS  PubMed  Google Scholar 

  37. Maisel, A. S. et al. Impact of age, race, and sex on the ability of B-type natriuretic peptide to aid in the emergency diagnosis of heart failure: results from the Breathing Not Properly (BNP) multinational study. Am. Heart J. 147, 1078–1084 (2004).

    Article  CAS  PubMed  Google Scholar 

  38. Krauser, D. G. et al. Neither race nor gender influences the usefulness of amino-terminal pro-brain natriuretic peptide testing in dyspneic subjects: a ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) substudy. J. Card. Fail. 12, 452–457 (2006).

    Article  CAS  PubMed  Google Scholar 

  39. Maffei, S., Del Ry, S., Prontera, C. & Clerico, A. Increase in circulating levels of cardiac natriuretic peptides after hormone replacement therapy in postmenopausal women. Clin. Sci. 101, 447–453 (2001).

    Article  CAS  Google Scholar 

  40. Lam, C. S. et al. Influence of sex and hormone status on circulating natriuretic peptides. J. Am. Coll. Cardiol. 58, 618–626 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Costello-Boerrigter, L. C. et al. Amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide in the general community: determinants and detection of left ventricular dysfunction. J. Am. Coll. Cardiol. 47, 345–353 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Chang, A. Y. et al. Associations among androgens, estrogens, and natriuretic peptides in young women: observations from the Dallas Heart Study. J. Am. Coll. Cardiol. 49, 109–116 (2007).

    Article  CAS  PubMed  Google Scholar 

  43. Hsich, E. M. et al. Relationship between sex, ejection fraction, and B-type natriuretic peptide levels in patients hospitalized with heart failure and associations with inhospital outcomes: findings from the Get With The Guideline-Heart Failure Registry. Am. Heart J. 166, 1063–1071.e3 (2013).

    Article  CAS  PubMed  Google Scholar 

  44. Hsich, E. M. & Pina, I. L. Heart failure in women: a need for prospective data. J. Am. Coll. Cardiol. 54, 491–498 (2009).

    Article  PubMed  Google Scholar 

  45. Fonarow, G. C., Peacock, W. F., Phillips, C. O., Givertz, M. M. & Lopatin, M. Admission B-type natriuretic peptide levels and in-hospital mortality in acute decompensated heart failure. J. Am. Coll. Cardiol. 49, 1943–1950 (2007).

    Article  CAS  PubMed  Google Scholar 

  46. Bursi, F. et al. Systolic and diastolic heart failure in the community. JAMA 296, 2209–2216 (2006).

    Article  CAS  PubMed  Google Scholar 

  47. Fonarow, G. C. et al. Usefulness of B-type natriuretic peptide and cardiac troponin levels to predict in-hospital mortality from ADHERE. Am. J. Cardiol. 101, 231–237 (2008).

    Article  CAS  PubMed  Google Scholar 

  48. Paulus, W. J. et al. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur. Heart J. 28, 2539–2550 (2007).

    Article  PubMed  Google Scholar 

  49. Hsich, E. M. et al. Sex differences in in-hospital mortality in acute decompensated heart failure with reduced and preserved ejection fraction. Am. Heart J. 163, 430–437 (2012).

    Article  PubMed  Google Scholar 

  50. Knudsen, C. W. et al. Diagnostic value of a rapid test for B-type natriuretic peptide in patients presenting with acute dyspnoe: effect of age and gender. Eur. J. Heart Fail. 6, 55–62 (2004).

    Article  CAS  PubMed  Google Scholar 

  51. Meyer, L. et al. Incidence, causes, and survival trends from cardiovascular-related sudden cardiac arrest in children and young adults 0 to 35 years of age: a 30-year review. Circulation 126, 1363–1372 (2012).

    Article  PubMed  Google Scholar 

  52. Christ, M. et al. Gender-specific risk stratification with B-type natriuretic peptide levels in patients with acute dyspnea: insights from the B-type natriuretic peptide for acute shortness of breath evaluation study. J. Am. Coll. Cardiol. 48, 1808–1812 (2006).

    Article  CAS  PubMed  Google Scholar 

  53. McDonagh, T. A. et al. Biochemical detection of left-ventricular systolic dysfunction. Lancet 351, 9–13 (1998).

    Article  CAS  PubMed  Google Scholar 

  54. Ledwidge, M. et al. Natriuretic peptide-based screening and collaborative care for heart failure: the STOP-HF randomized trial. JAMA 310, 66–74 (2013).

    Article  CAS  PubMed  Google Scholar 

  55. Greenland, P. et al. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 122, e584–e636 (2010).

    PubMed  Google Scholar 

  56. Moller, N. & Jorgensen, J. O. Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocr. Rev. 30, 152–177 (2009).

    Article  CAS  PubMed  Google Scholar 

  57. Hallengren, E. et al. Fasting levels of high-sensitivity growth hormone predict cardiovascular morbidity and mortality: the Malmö Diet and Cancer study. J. Am. Coll. Cardiol. 64, 1452–1460 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Pincus, S. M. et al. Females secrete growth hormone with more process irregularity than males in both humans and rats. Am. J. Physiol. 270, E107–E115 (1996).

    Article  CAS  PubMed  Google Scholar 

  59. Hindmarsh, P. C. et al. A sexually dimorphic pattern of growth hormone secretion in the elderly. J. Clin. Endocrinol. Metab. 84, 2679–2685 (1999).

    Article  CAS  PubMed  Google Scholar 

  60. Veldhuis, J. D., Roelfsema, F., Keenan, D. M. & Pincus, S. Gender, age, body mass index, and IGF-I individually and jointly determine distinct GH dynamics: analyses in one hundred healthy adults. J. Clin. Endocrinol. Metab. 96, 115–121 (2011).

    Article  CAS  PubMed  Google Scholar 

  61. Dumic, J., Dabelic, S. & Flogel, M. Galectin-3: an open-ended story. Biochim. Biophys. Acta 1760, 616–635 (2006).

    Article  CAS  PubMed  Google Scholar 

  62. de Boer, R. A., Voors, A. A., Muntendam, P., van Gilst, W. H. & van Veldhuisen, D. J. Galectin-3: a novel mediator of heart failure development and progression. Eur. J. Heart Fail. 11, 811–817 (2009).

    Article  CAS  PubMed  Google Scholar 

  63. Ueland, T. et al. Galectin-3 in heart failure: high levels are associated with all-cause mortality. Int. J. Cardiol. 150, 361–364 (2011).

    Article  PubMed  Google Scholar 

  64. Tang, W. H. et al. Usefulness of plasma galectin-3 levels in systolic heart failure to predict renal insufficiency and survival. Am. J. Cardiol. 108, 385–390 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Gopal, D. M. et al. Relationship of plasma galectin-3 to renal function in patients with heart failure: effects of clinical status, pathophysiology of heart failure, and presence or absence of heart failure. J. Am. Heart Assoc. 1, e000760 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. O'Seaghdha, C. M. et al. Elevated galectin-3 precedes the development of CKD. J. Am. Soc. Nephrol. 24, 1470–1477 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. de Boer, R. A. et al. The fibrosis marker galectin-3 and outcome in the general population. J. Intern. Med. 272, 55–64 (2012).

    Article  CAS  PubMed  Google Scholar 

  68. Daniels, L. B., Clopton, P., Laughlin, G. A., Maisel, A. S. & Barrett-Connor, E. Galectin-3 is independently associated with cardiovascular mortality in community-dwelling older adults without known cardiovascular disease: the Rancho Bernardo Study. Am. Heart J. 167, 674–682.e1 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Ho, J. E. et al. Galectin-3, a marker of cardiac fibrosis, predicts incident heart failure in the community. J. Am. Coll. Cardiol. 60, 1249–1256 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Daniels, L. B. & Bayes-Genis, A. Using ST2 in cardiovascular patients: a review. Future Cardiol. 10, 525–539 (2014).

    Article  CAS  PubMed  Google Scholar 

  71. Dieplinger, B. et al. Soluble ST2 is not independently associated with androgen and estrogen status in healthy males and females. Clin. Chem. Lab. Med. 49, 1515–1518 (2011).

    Article  CAS  PubMed  Google Scholar 

  72. Coglianese, E. E. et al. Distribution and clinical correlates of the interleukin receptor family member soluble ST2 in the Framingham Heart Study. Clin. Chem. 58, 1673–1681 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Kim, E. S., Carrigan, T. P. & Menon, V. Enrollment of women in National Heart, Lung, and Blood Institute-funded cardiovascular randomized controlled trials fails to meet current federal mandates for inclusion. J. Am. Coll. Cardiol. 52, 672–673 (2008).

    Article  PubMed  Google Scholar 

  74. Harris, D. J. & Douglas, P. S. Enrollment of women in cardiovascular clinical trials funded by the National Heart, Lung, and Blood Institute. N. Engl. J. Med. 343, 475–480 (2000).

    Article  CAS  PubMed  Google Scholar 

  75. Melloni, C. et al. Representation of women in randomized clinical trials of cardiovascular disease prevention. Circ. Cardiovasc. Qual. Outcomes 3, 135–142 (2010).

    Article  PubMed  Google Scholar 

  76. Mosca, L. et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women--2011 update: a guideline from the American Heart Association. J. Am. Coll. Cardiol. 57, 1404–1423 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  77. Carraway, R. & Leeman, S. E. The isolation of a new hypotensive peptide, neurotensin, from bovine hypothalami. J. Biol. Chem. 248, 6854–6861 (1973).

    CAS  PubMed  Google Scholar 

  78. Reinecke, M. Neurotensin. Immunohistochemical localization in central and peripheral nervous system and in endocrine cells and its functional role as neurotransmitter and endocrine hormone. Prog. Histochem. Cytochem. 16, 1–172 (1985).

    Article  CAS  PubMed  Google Scholar 

  79. Baca, I. et al. Effect of neurotensin on exocrine pancreatic secretion in dogs. Digestion 23, 174–183 (1982).

    Article  CAS  PubMed  Google Scholar 

  80. Andersson, S., Rosell, S., Hjelmquist, U., Chang, D. & Folkers, K. Inhibition of gastric and intestinal motor activity in dogs by (Gln4) neurotensin. Acta Physiol. Scand. 100, 231–235 (1977).

    Article  CAS  PubMed  Google Scholar 

  81. Armstrong, M. J., Parker, M. C., Ferris, C. F. & Leeman, S. E. Neurotensin stimulates [3H]oleic acid translocation across rat small intestine. Am. J. Physiol. 251, G823–G829 (1986).

    CAS  PubMed  Google Scholar 

  82. Tyler-McMahon, B. M., Boules, M. & Richelson, E. Neurotensin: peptide for the next millennium. Regul. Pept. 93, 125–136 (2000).

    Article  CAS  PubMed  Google Scholar 

  83. Wu, Z., Martinez-Fong, D., Tredaniel, J. & Forgez, P. Neurotensin and its high affinity receptor 1 as a potential pharmacological target in cancer therapy. Front. Endocrinol. (Lausanne) 3, 184 (2012).

    Google Scholar 

  84. Bean, A. J., Dagerlind, A., Hokfelt, T. & Dobner, P. R. Cloning of human neurotensin/neuromedin N genomic sequences and expression in the ventral mesencephalon of schizophrenics and age/sex matched controls. Neuroscience 50, 259–268 (1992).

    Article  CAS  PubMed  Google Scholar 

  85. Barelli, H. et al. Role of endopeptidase 3.4.24.16 in the catabolism of neurotensin, in vivo, in the vascularly perfused dog ileum. Br. J. Pharmacol. 112, 127–132 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Checler, F., Vincent, J. P. & Kitabgi, P. Neuromedin N: high affinity interaction with brain neurotensin receptors and rapid inactivation by brain synaptic peptidases. Eur. J. Pharmacol. 126, 239–244 (1986).

    Article  CAS  PubMed  Google Scholar 

  87. Friry, C., Feliciangeli, S., Richard, F., Kitabgi, P. & Rovere, C. Production of recombinant large proneurotensin/neuromedin N-derived peptides and characterization of their binding and biological activity. Biochem. Biophys. Res. Commun. 290, 1161–1168 (2002).

    Article  CAS  PubMed  Google Scholar 

  88. Ernst, A., Hellmich, S. & Bergmann, A. Proneurotensin 1–117, a stable neurotensin precursor fragment identified in human circulation. Peptides 27, 1787–1793 (2006).

    Article  CAS  PubMed  Google Scholar 

  89. Melander, O. et al. Plasma proneurotensin and incidence of diabetes, cardiovascular disease, breast cancer, and mortality. JAMA 308, 1469–1475 (2012).

    Article  CAS  PubMed  Google Scholar 

  90. Melander, O. et al. Validation of plasma proneurotensin as a novel biomarker for the prediction of incident breast cancer. Cancer Epidemiol. Biomarkers Prev. 23, 1672–1676 (2014).

    Article  CAS  PubMed  Google Scholar 

  91. Fawad, A., Schultz, C., Nilsson, P., Orho-Melander, M. & Melander, O. Proneurotensin independently predicts cardiovascular disease—the Malmö Preventive Project. Presented at the 25th European Meeting on Hypertension and Cardiovascular Protection.

Download references

Author information

Authors and Affiliations

  1. Division of Cardiovascular Medicine, University of California, 9444 Medical Center Drive, La Jolla, 92037-7411, CA, USA

    Lori B. Daniels & Alan S. Maisel

Authors
  1. Lori B. Daniels
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alan S. Maisel
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Both authors researched data for the article, discussed its content, wrote the manuscript, and reviewed/edited it before submission.

Corresponding author

Correspondence to Lori B. Daniels.

Ethics declarations

Competing interests

L.B.D. declares that she has received speaking fees from Critical Diagnostics and Roche Diagnostics, and has served as a consultant for diaDexus. A.S.M. declares that he has received research support from Abbott, Alere, Critical Diagnostics, ResMed, Roche Diagnostics, and Sphingotec; and consulting fees from Alere, BG Medicine, Critical Diagnostics, diaDexus, and Sphingotec.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Daniels, L., Maisel, A. Cardiovascular biomarkers and sex: the case for women. Nat Rev Cardiol 12, 588–596 (2015). https://doi.org/10.1038/nrcardio.2015.105

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrcardio.2015.105

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing