Skip Navigation

European Journal of Heart Failure 2005 7(5):859-864; doi:10.1016/j.ejheart.2005.01.017
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
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 Varela-Roman, A.
Right arrow Articles by Gonzalez-Juanatey, J. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Varela-Roman, A.
Right arrow Articles by Gonzalez-Juanatey, J. R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2005 European Society of Cardiology

Influence of diabetes on the survival of patients hospitalized with heart failure: A 12-year study

Alfonso Varela-Roman, Lilian Grigorian Shamagian, Eduardo Barge Caballero, Pilar Mazon Ramos, Pedro Rigueiro Veloso and Jose Ramon Gonzalez-Juanatey*

Santiago de Compostela Spain

* Corresponding author. Present address: Servicio de Cardiologia, Hospital Clinico de Santiago de Compostela, Spain. Tel.: +34 981 950 757; fax: +34 981 950 754. E-mial address: jose.ramon.gonzalez.juanatey{at}sergas.es


   Abstract
Top
 Abstract
1. Introduction
 2. Patients and methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 
Aim: To investigate the influence of diabetes mellitus (DM) on the prognosis of heart failure (HF) patients, focussing specifically on aetiology and patients with preserved left ventricular systolic function (LVSF), which to date has not been fully investigated.

Method and results: 1659 Patients hospitalized for HF between 1991 and 2002 in the Cardiology Department of a tertiary hospital, aged 69±12years, 60% male were studied prospectively. Arterial hypertension was present in 54% of patients, DM in 26% and ischaemic cardiomyopathy in 51%. A survival analysis performed in April 2003 showed that DM worsens the prognosis of the whole group (median survival (MS):3.6 vs. 5.4 years; p<0.001), of ischaemic and non-ischaemic patients (MS: 3.8 vs. 4.9 years; p=0.13 and 3.6 vs. 6.0 years; p<0.001, respectively). A similar effect of DM was shown in patients with preserved LVSF (MS: 3.8 vs. 5.8 years; p=0.03) and in patients with impaired LVSF (3.6 vs. 6.3 years; p<0.0001).

Conclusion: DM increases mortality among HF patients with preserved and impaired LVSF and those without ischaemic cardiomyopathy.

Key Words: Heart failure • Diabetes mellitus • Prognosis

Received July 1, 2004; Revised October 27, 2004; Accepted January 27, 2005


   1. Introduction
Top
 Abstract
 1. Introduction
2. Patients and methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 
Although there are differences between the results of clinical trials and studies that include a broader range of patients, the prevalence of diabetes mellitus among patients with heart failure (HF) is about 20% [1–4], compared with 4–6% in the general population [5]. Reciprocally, epidemiological studies have shown that diabetes increases the risk of developing HF [6], and the worse the diabetic control, the greater is the risk [7]. Several randomized clinical trials have shown that diabetes also increases morbidity and mortality in patients with HF [8]. It has been suggested that the impact of diabetes on the prognosis of HF patients may be limited to patients with ischaemic cardiomyopathy [9], however, this issue has not yet been resolved. It is also uncertain whether the impact of diabetes is dependent on the presence or absence of left ventricular systolic dysfunction. Most information about the impact of diabetes on the prognosis of HF patients has come from clinical trials, in which ischaemic patients have predominated over non-ischaemic patients, and patients with LVSD over patients with preserved systolic function [9,10]. There have been very few reports on patients with preserved systolic function in study groups more representative of the general HF population.

In this study, we investigated the effect of diabetes mellitus on survival in an unselected group of patients hospitalized with HF, distinguishing between ischaemic and non-ischaemic aetiology and the presence or absence of left ventricular systolic dysfunction.


   2. Patients and methods
Top
 Abstract
 1. Introduction
 2. Patients and methods
3. Results
 4. Discussion
 5. Conclusions
 References
 
2.1. Study groups
The whole study group comprised 1659 HF patients admitted to the Cardiology Department of our tertiary hospital between January 1st, 1991, and December 31st, 2002. HF was defined according to the modified Framingham criteria: satisfaction of two or more major criteria (paroxysmal nocturnal dyspnea, orthopnea, rales, jugular venous distension, third sound, and radiological signs of pulmonary congestion and/or cardiomegaly) or of one major criterion together with two or more minor criteria (effort dyspnea, peripheral oedema, hepatomegaly, and pleural effusion). For patients admitted on more than one occasion, only the data acquired upon first admission were included in this study. The diabetic subgroup comprised 442 patients who were receiving or needed treatment with insulin or oral hypoglycaemic agents to control glycaemia, or while hospitalized had fasting blood glucose levels >126 mg/dL or non-fasting levels >200 mg/dL.

2.2. Data collection
Demographic and clinical characteristics, results of laboratory and other tests, and treatment prescribed upon release from hospital were recorded for each patient. Survival data were obtained in April 2003 by searching the general archives of the Hospital and by a telephone survey. Survival data were obtained for 1493 patients (90%), with a mean follow-up time of 3.13±2.76 years (range 0.00–12.21 years).

2.3. Substudies
Two substudies were also performed. The first was to investigate whether the influence of diabetes on survival was dependent on whether HF was of ischaemic origin (841 patients) or non-ischaemic origin (818 patients). HF was deemed to be of ischaemic origin if the patient had a prior diagnosis of ischaemic cardiomyopathy, had previously been admitted for an acute coronary event (adequately diagnosed unstable angina or myocardial infarction), had previously undergone surgical or percutaneous myocardial revascularization; if the EKG obtained during the hospital admission displayed pathological Q waves; or if coronary images obtained at that time displayed >50% stenosis of at least one coronary vessel.

The second substudy included only the 1252 patients whose left ventricular ejection fraction (EF) was determined by echocardiography during the hospital admission. This substudy investigated whether the influence of diabetes on survival was dependent on whether left ventricular systolic function was preserved (EF≥0.50; 498 patients) or impaired (EF<0.50; 754 patients).

2.4. Statistical analyses
Data for categorical or dichotomous variables are expressed as percentages and were compared using a Chi-squared test. Data for continuous variables are expressed as means ±standard deviations and were compared using student's t tests. Survival curves for subgroups and for the whole sample were estimated by the Kaplan–Meier method and were compared pairwise using the two-sample log rank test or Breslow's test. Factors with independent significant association with survival were identified using Cox's proportional hazards model in a backward stepwise regression analysis with age, sex, NYHA class, jugular vein distension, alveolar oedema, hypertension, hyperlipidaemia, atrial fibrillation, EF and diabetes as independent variables, followed by a secondary Cox analysis in which the independent variables were those identified as significant in the first analysis plus diabetes. The resulting regression coefficients were used to estimate relative risks and the corresponding 95% confidence intervals. The validity of the assumption of proportional hazards was supported by the results of calculating log–log survival plots for each variable with age and sex controlled. The criterion for statistical significance was p<0.05.


   3. Results
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
4. Discussion
 5. Conclusions
 References
 
3.1. Characteristics of the whole study group
The whole study group comprised 1659 patients, of these 60% were male and the mean age was 70 years (Table 1). The most prevalent risk factor for HF, arterial hypertension, was identified in slightly more than half of these patients, and diabetes mellitus in just over a quarter. The most prevalent aetiology was ischaemic cardiomyopathy (51% of cases). The non-ischaemic aetiologies were valve disease (314 patients, 18.9%), dilated cardiomyopathy (135, 8.1%), and others (369, 22.2%). Almost a third of patients showed atrial fibrillation. Echocardiography was performed in just over 80% of cases (1330 patients) of these EF was determined in 1252 patients. The remaining 78 patients underwent echocardiography but it was not possible to determine their EF. Among the patients whose EF was determined, almost 40% had preserved left ventricular systolic function.


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

  		Table 1 Characteristics of 1659 patients hospitalized for HF between 1991 and 2002

 
3.2. Characteristics of the diabetic and non-diabetic subgroups
The clinical, radiological and therapeutic characteristics of the diabetic and non-diabetic subgroups were in general very similar, but showed the differences reported in previous studies. In particular, the diabetic group had a greater proportion of women and a higher prevalence of hypertension, hyperlipidaemia and ischaemic cardiomyopathy (especially three-vessel disease), while the non-diabetic group were more frequently smokers and were more prone to atrial fibrillation (Table 1).

3.3. Predictors of mortality in the whole study group
Following adjustment for hypertension, hyperlipidaemia, sex, NYHA class, EF, and atrial fibrillation, diabetes was the second most influential independent predictor of death in the whole sample, behind alveolar oedema but ahead of jugular vein distension and a 1-year increase in age (Table 2).


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

  		Table 2 Variables with independent influence on the survival of HF patients in a multivariate analysis after adjustment for the effects of hypertension, hyperlipidaemia, sex, NYHA class, ejection fraction and atrial fibrillation

 
3.4. Survival in the diabetic and non-diabetic groups
In the non-diabetic group, there were seven factors showing significant association with increased risk of death in univariate analyses (age, rales, alveolar oedema, ischaemic cardiomyopathy, clinical severity (NYHA class), systemic congestion, and pleural effusion), however, for the diabetic group there were only four (age, rales, alveolar oedema, and atrial fibrillation). Treatment with ACE inhibitors and treatment with β-blockers were both associated with increased survival among both diabetics and non-diabetics.

Survival rates after 1, 3 and 5 years, as determined by the Kaplan–Meier method, were significantly lower among diabetics: 78.9%, 57.2% and 39.0%, respectively, than among non-diabetics, 84.7%, 68.3% and 52.7% (Fig. 1). Median survival time in the diabetic group was 3.62 years (95% CI 3.02–4.22 years), as against 5.42 years (95% CI 4.70–6.14 years) in the non-diabetic group.


Figure 1
View larger version (9K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1 Kaplan–Meier survival curves of 442 diabetic (DM) and 1217 non-diabetic (non-DM) patients hospitalized with HF.

 
3.5. Influence of diabetes on the survival of ischaemic and non-ischaemic patients
Diabetes reduced the survival of both ischaemic and non-ischaemic patients, but its influence was more marked among the latter. Median survival times were 3.77 years (95% CI 3.02–4.52 years) for diabetics as against 4.87 years (95% CI 3.90–5.84 years) for non-diabetics in the ischaemic group (relative risk=1.18), and 3.56 years (95% CI 2.37–4.76 years) for diabetics as against 5.96 years (95% CI 4.67–7.26 years) for non-diabetics in the non-ischaemic group (relative risk=1.63). In keeping with this, the Kaplan–Meier survival curve for diabetics differed significantly from that of non-diabetics in the non-ischaemic group, but not in the ischaemic group (Fig. 2). Also, multivariate analysis following adjustment for the same variables as for the whole sample (see above) showed diabetes (RR 1.687, p=0.003), age (p<0.001) and jugular vein distension (p=0.021) to be independent predictors of death in the non-ischaemic group, whereas the only independent predictor in the ischaemic group was age.


Figure 2
View larger version (9K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 2 Kaplan–Meier survival curves of diabetic (DM) and non-diabetic (non-DM) subgroups of HF patients hospitalized with (n=841) and without (n=818) ischaemic cardiomyopathy.

 
3.6. Influence of diabetes on survival in groups with preserved and impaired systolic function
Diabetes reduced the survival of both patients with preserved systolic function (EF≥50%) and patients with impaired systolic function, but its influence was more marked among the latter. Median survival times were 3.84 years (95% CI 2.46–5.21 years) for diabetics compared with 5.83 years (95% CI 4.35–7.31 years) for non-diabetics in the group with preserved systolic function. In the group with impaired systolic function, median survival times were 3.56 years (95% CI 3.04–4.07 years) for diabetics and 6.32 years (95% CI 5.00–7.63 years) for non-diabetics. The Kaplan–Meier survival curve for diabetics differed more significantly from that of non-diabetics in the impaired systolic function group than in the preserved systolic function group (Fig. 3).


Figure 3
View larger version (8K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 3 Kaplan–Meier survival curves of diabetic (DM) and non-diabetic (non-DM) subgroups HF patients hospitalized with left ventricular ejection fractions ≥50% (n=498) and <50% (n=754).

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
 4. Discussion
5. Conclusions
 References
 
In this study of patients hospitalized with HF, diabetes reduced survival significantly in the absence of ischaemia (but not in its presence), and in both the presence and absence of left ventricular systolic dysfunction.

The relationship between diabetes mellitus and HF is multifactorial and in all probability reciprocal: diabetes increases the risk of developing HF [6] and HF seems to increase the risk of developing diabetes [11]. In the latter regard, the physiopathological changes involved in HF appear to hinder peripheral uptake of glucose, possibly by increasing insulin resistance [12]. In the former, several studies have found diabetes to increase both the risk of developing HF and the death rate among HF patients [8], however, studies of the effect of diabetes on mortality are limited to patients with left ventricular systolic dysfunction. The present findings show that the survival of HF patients with preserved systolic function is also reduced by diabetes.

The prognosis of HF with preserved systolic function remains controversial. Although certain studies have found mortality among HF patients to be significantly greater when systolic function is impaired than when it is preserved [13–15], most of these studies have included patients whose HF was diagnosed at community care level. Most studies showing that impaired systolic function has no significant effect on survival have included only hospitalized patients [16–18]. The present results are in agreement with the latter studies, showing the deleterious effect of diabetes on the survival of HF patients in general, in both patients hospitalized with systolic dysfunction and those with preserved systolic function. The influence of diabetes was more marked in the functionally impaired group than in the functionally preserved group, as compared to the non-diabetics in whom left ventricular systolic functional status was not significantly associated with mortality.

In the present study, diabetes increased mortality significantly among non-ischaemic patients but not among ischaemic patients. However, in several clinical trials, the reverse has been observed. In particular, in the SOLVD and BEST studies [9,10], diabetes increased the relative risk of mortality among ischaemic patients by factors of 1.37 (95% CI 1.21–1.55) and 1.33 (95% CI 1.12–1.58) respectively, but had no significant effect on the survival of non-ischaemic patients. Similarly, a recently published 10-year study of HF patients referred for evaluation of left ventricular dysfunction found that diabetes shortened the survival of ischaemic patients but, depending on the definition of diabetes, either did not affect or actually lengthened the survival of non-ischaemics [19].

Several plausible hypotheses may be put forward to explain why diabetes should affect ischaemic patients more than non-ischaemic patients (for example, by increasing the risk of plaque rupture among patients with atheromas). The finding that diabetes appeared to have no significant effect on non-ischaemic patients in the SOLVD and BEST trials may have been due to the relatively small numbers of non-ischaemic patients included in these studies. In addition, in view of the insensitivity of the criteria used to define diabetes (self-report or mention in medical records), the non-diabetic groups may in fact have included a number of diabetic patients. In the study by de Groote et al. [19], it may be relevant that all patients (ischaemic or not) exhibited left ventricular dysfunction (EF<45%), all were stable, 85% were male, few were in NYHA classes III or IV (28%), and their death rate was relatively low (about 35% at 5 years).

The failure of the present study to detect a significant effect of diabetes in the ischaemic group may have been due to the fact that mortality was higher among our patients than in the SOLVD, BEST or de Groote studies, which may have resulted in lack of sufficient statistical power (note that whereas ischaemia had virtually no effect on the survival of diabetics, it considerably reduced that of non-diabetics). In view of the known deleterious effects of diabetes on the kidney and the cardiovascular system, it seems probable that, if the survival rate among our ischaemic patients as a group had been as high as in the studies mentioned above, we too would have observed a significant effect of diabetes on mortality in this group.


   5. Conclusions
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
 4. Discussion
 5. Conclusions
References
 
Diabetes mellitus increases mortality among HF patients with preserved systolic function, those with systolic dysfunction, and those without ischaemic cardiomyopathy. Although in this study diabetes did not significantly increase mortality among HF patients with ischaemic cardiomyopathy, this may have been due to lack of statistical power.


   References
Top
 Abstract
 1. Introduction
 2. Patients and methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 

  1. Zannad F., Braincon S., Juilliere Y., Mertes P.M., Villemot J.P., Alla F., et al. Incidence, clinical and etiologic features, and outcomes of advanced chronic heart failure: the EPICAL Study. Epidemiologie de l'Insuffisance Cardiaque Avancee en Lorraine. J Am Coll Cardiol (1999) 33:734–742.[Abstract/Free Full Text]
  2. Shindler D.M., Kostis J.B., Yusuf S., Quinones M.A., Pitt B., Stewart D., et al. Diabetes mellitus, a predictor of morbidity and mortality in the studies of left ventricular dysfunction (SOLVD) trials and registry. Am J Cardiol (1996) 77:1017–1020.[CrossRef][Web of Science][Medline]
  3. Ryden L., Armstrong P.W., Cleland J.G., Horowitz J.D., Massie B.M., Packer M., et al. Efficacy and safety of high-dose lisinopril in chronic heart failure patients at high cardiovascular risk, including those with diabetes mellitus. Results from the ATLAS trial. Eur Heart J (2000) 21:1967–1978.[Abstract/Free Full Text]
  4. Gonzalez-Juanatey J.R., Alegria Ezquerra E., Garcia Acuña M.J., Gonzalez Maqueda I., Vicente Lozano J. The role of diabetes mellitus in cardiac disease in Spain. The CARDIOTENS study 1999. Med Clin (2001) 116:686–691.
  5. King H., Aubert R.E., Herman W.H. Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care (1998) 21:1414–1431.[Abstract]
  6. Kannel W.B., McGee D.L. Diabetes and cardiovascular disease. The Framingham study. JAMA (1979) 241:2035–2038.[Abstract/Free Full Text]
  7. Stratton I.M., Adler A.I., Neil H.A., Matthews D.R., Manley S.E., Cull C.A., et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ (2000) 321:405–412.[Abstract/Free Full Text]
  8. Solang L., Malmberg K., Ryden L. Diabetes mellitus and congestive heart failure. Further knowledge needed. Eur Heart J (1999) 20:789–795.[Free Full Text]
  9. Domanski M., Krause-Steinrauf H., Deedwania P., et al. The effect of diabetes on outcomes of patients with advanced heart failure in the BEST trial. J Am Coll Cardiol (2003) 42:914–922.[Abstract/Free Full Text]
  10. Dries D., Sweitzer N., Drazner M., Stevenson L.W., Gersh B.J. Prognostic impact of diabetes mellitus in patients with heart failure according to the etiology of left ventricular dysfunction. J Am Coll Cardiol (2001) 38:421–428.[Abstract/Free Full Text]
  11. Amato L., Paolisso G., Cacciatore F., Ferrara N., Ferrara P., Canonico S., et al. Congestive heart failure predicts the development of non-insulin-dependent diabetes mellitus in the elderly. The Osservatorio Geriatrico Regione Campania Group. Diabetes Metab (1997) 23:213–218.[Web of Science][Medline]
  12. Swan J.W., Anker S.D., Walton C., Godsland I.F., Clark A.L., Leyva F., et al. Insulin resistance in chronic heart failure: relation to severity and etiology of heart failure. J Am Coll Cardiol (1997) 30:527–532.[Abstract]
  13. Vasan R.S., Larson M.G., Benjamin E.J., Evans J.C., Reiss C.K., Levy D. Congestive heart failure in subjects with normal versus reduced left ventricular ejection fraction. J Am Coll Cardiol (1999) 33:1948–1955.[Abstract/Free Full Text]
  14. Smith G.L., Masoudi F.A., Vaccarino V., Radford M.J., Krumholz H.M. Outcomes in heart failure patients with preserved ejection fraction: mortality, readmission and functional decline. J Am Coll Cardiol (2003) 41:1519–1522.[Free Full Text]
  15. Ghali J.K., Kadakia S., Bhatt A., Cooper R., Liao Y. Survival of heart failure with preserved versus impaired systolic function: the prognostic implication of blood pressure. Am Heart J (1992) 123:993–997.[CrossRef][Web of Science][Medline]
  16. Senni M., Tribouilloy C.M., Rodeheffer R.J., et al. Congestive heart failure in the community. A study of all incident cases in Olmsted Country, Minnesota in 1991. Circulation (1998) 98:2282–2289.[Abstract/Free Full Text]
  17. McDermott M.M., Feinglass J., Sy J., Gheorghiade M. Hospitalized congestive heart failure patients with preserved versus abnormal left ventricular systolic function: clinical characteristics and drug therapy. Am J Med (1995) 99:629–635.[CrossRef][Web of Science][Medline]
  18. Varela-Roman A., Gonzalez-Juanatey J.R., Basante P., et al. Clinical characteristics and prognosis of hospitalised in patients with heart failure and preserved or reduced left ventricular ejection fraction. Heart (2002) 88:249–254.[Abstract/Free Full Text]
  19. De Groote P., Lamblin N., Mouquet F., Plichon D., McFadden E., Van Belle E., et al. Impact of diabetes mellitus on long-term survival in patients with congestive heart failure. Eur Heart J (2004) 25:656–662.[Abstract/Free Full Text]

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
 Am. J. Physiol. Heart Circ. Physiol.Home page
S. Matsushima, S. Kinugawa, T. Yokota, N. Inoue, Y. Ohta, S. Hamaguchi, and H. Tsutsui
Increased myocardial NAD(P)H oxidase-derived superoxide causes the exacerbation of postinfarct heart failure in type 2 diabetes
Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H409 - H416.
[Abstract] [Full Text] [PDF]

Home page
 HeartHome page
C Tribouilloy, D Rusinaru, H Mahjoub, J-M Tartiere, L Kesri-Tartiere, S Godard, and M Peltier
Prognostic impact of diabetes mellitus in patients with heart failure and preserved ejection fraction: a prospective five-year study
Heart, November 1, 2008; 94(11): 1450 - 1455.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
H. Tominaga, H. Katoh, K. Odagiri, Y. Takeuchi, H. Kawashima, M. Saotome, T. Urushida, H. Satoh, and H. Hayashi
Different effects of palmitoyl-L-carnitine and palmitoyl-CoA on mitochondrial function in rat ventricular myocytes
Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H105 - H112.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
E. Erdmann and R. G. Wilcox
Weighing up the cardiovascular benefits of thiazolidinedione therapy: the impact of increased risk of heart failure
Eur. Heart J., January 1, 2008; 29(1): 12 - 20.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
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 Varela-Roman, A.
Right arrow Articles by Gonzalez-Juanatey, J. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Varela-Roman, A.
Right arrow Articles by Gonzalez-Juanatey, J. R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?