Heart Failure
Table 3: Baseline Demographic and Clinical Characteristics of the Study Population by Quartile of Galectin-3 Level Baseline Characteristic
All Subjects (n=232)
1 (
Age, mean (SD) (years) Male (%)
Ischaemic aetiology (%)
NYHA functional class (%) III IV
LVEF, mean (SD)
BMI, mean (SD), kg/m2 Diabetes (%) COPD (%)
Smoker (%) GFR, mean (SD), ml/min
NT-proBNP level, mean (SD), pmol/l Galectin-3 level, mean (SD), ng/ml
70.9 (10) 72.4 62.5
96 4
30.9 (9.4) 26.3 (4.7) 30 29 13
55 (22.8)
456 (616.7) 18.6 (7.8)
64.6 (11.7) 72.4 50
97 2
31.1 (10) 27.9 (5.3) 28 25 17
72.7 (24.5)
291.1 (376.6) 11.3 (1.6)
Galectin-3 Quartile (ng/ml) 2 (13.63–17.63)
n=59
71.6 (8.9) 76.3 70.2
100 0
29.7 (8.2) 25.9 (4.1) 22 23 12
56 (18.6)
353.8 (386.7) 15.5 (1.3)
3 (17.64–21.62) n=57
72.8 (8.9) 68.4 61
93 6
31.9 (8.7) 25.8 (4.7) 35 32 14
49.2 (19.4)
526.5 (561.1) 19.5 (1.2)
4 (>21.62) n=58
74.6 (7) 72.4 69
93 7
31 (10.6) 25.9 (4.3) 33 35 9
42.3 (16.6)
651.2 (920.4) 28.2 (9)
Percentages may not total 100 due to rounding. p-values are from one-way analysis of variance (ANOVA) comparison of means across quartiles of galectin-3. BMI = body mass index; GFR = glomerular filtration rate; COPD = chronic obstructive pulmonary disease; LVEF = left ventricular ejection fraction; NS = not significant; NT-proBNP = N-terminal prohormone brain natriuretic peptide; NYHA = New York Heart Association; SD = standard deviation.
et al. recently investigated the prognostic value of Gal-3 in this cohort, extending an all-cause mortality follow-up for up to 6.5 years with a mean follow-up of 4.0±1.9 years. The baseline characteristics of the population by Gal-3 quartiles are shown in Table 3. Progressively higher levels of Gal-3 were associated with increased age, worse renal function, lower BMI and higher NT-proBNP levels. Overall, Gal-3 remained an independent predictor of mortality in these stable HF patients (Gal-3 hazard ratio 1.24, 95% confidence interval 1.03–1.5 after adjustment for age, gender, renal function and NT-proBNP).13
A second recent evaluation of chronic HF patients, the Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart failure (COACH), examined another chronic HF population, and the results were presented at the 2009 HFSA. van Veldhuisen et al. measured Gal-3 in 592 patients with stable NYHA class II–IV HF with an LVEF
Conclusions and Future Directions for Galectin-3 in Heart Failure
Gal-3 is a protein that has been directly implicated in the inflammatory process and subsequent fibrosis in multiple organ systems, including
1. Lloyd-Jones D, et al., Circulation, 2010;121:e46–e215. 2. Fang J, et al., J Am Coll Cardiol, 2008;52:428–34. 3. Bleumink GS, et al., Eur Heart J, 2004;25:1614–19. 4. Solomon SD, et al., Circulation, 2007;116:1482–7. 5. Jencks SF, et al., N Engl J Med, 2009;360:1418–28.
the heart. Unlike markers such as the cardiac troponins or the natriuretic peptides, there is ample evidence that Gal-3 is directly involved in the pathophysiology of cardiac injury and progression to HF, making it a potential target for future therapy.
In this review specific case examples are shown and data are presented showing that Gal-3 could have an important complementary role to the established natriuretic peptide tests. Given what is known about its role in accelerating cardiac fibrosis and based on the statistical analysis from the studies outlined above, Gal-3 may ultimately be a more powerful prognosticator in the HF setting than the natriuretic peptides. Furthermore, although we are relatively early in the evaluation of Gal-3 as a cardiac biomarker, there now exists a robust ELISA that will allow testing in populations with more subtle manifestations of disease, with anticipated lower Gal-3 levels than those found in HF patients. Subsequent evaluation of Gal-3 in populations with ACC/AHA stage B (structural heart disease without symptoms) or even stage A (risk factors without structural heart disease or symptoms) may ultimately find a marker that identifies those who are at greatest risk of progressing to symptomatic HF. Lastly, and perhaps most intriguing, is the possibility that inhibition of the pro-fibrotic actions of Gal-3 may be a target for the prevention or treatment of HF. Ultimately, both of these scenarios are likely to be the subject of much future research with this new cardiac biomarker. n
6. Wilson Tang WH, et al., Circulation, 2007;116:e99–109. 7. Henderson NC, et al., Am J Pathol, 2008;172:288–98. 8. Sharma UC, et al., Circulation, 2004;110:3121–8. 9. Writing Committee, Circulation, 2009;119:e391–479. 10. Christenson RH, et al., Clin Biochem, 2010;43(7–8):683–90.
11. van Kimmenade RR, et al., J Am Coll Cardiol, 2006;48: 1217–24.
12. de Filippi CR, et al., J Card Fail, 2009;15(6):S9. 13. Lok DJ, et al., Clin Res Cardiol, 2010 (published online). 14. van Veldhuisen DJ, et al., J Card Fail, 2009;15:814.
0.047
NS NS NS
0.046 NS NS NS
p-value
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