Glucose abnormalities and heart failure : Epidemiological and therapeutic aspects

Abstract: Background The combination of heart failure and glucose abnormalities is seen with increasing frequency. The condition, which is characterised by low functional capacity and a high mortality, is very resource consuming. The link between glucose abnormalities and heart failure is complex. Improved knowledge is needed to describe the magnitude of the problem and to enable better risk stratification and patient management. Aims This thesis explores the relation between glucose abnormalities and heart failure from an epidemiological and a therapeutic perspective. Studies I-III The prevalence and incidence of glucose abnormalities and heart failure and their combination were studied in the Reykjavik Study, a large, population based cohort conducted 1967-1996. Cases were defined according to World Health Organization (WHO) criteria for type 2 diabetes mellitus/impaired glucose tolerance and the European Society of Cardiology (ESC) guidelines for heart failure. The overall prevalence of the combination of type 2 diabetes and heart failure was 0.5% in males and 0.4% in women while abnormal glucose regulation in combination with heart failure was found among 0.7% of men and 0.6% of women. The prevalence of glucose abnormalities and heart failure increased with age. The odds ratio of the association between type 2 diabetes and heart failure was 2.8 (95% Cl: 2.2-3.6) and between abnormal glucose regulation and heart failure 1.7 (95% Cl: 1.4-2.1 ). The incidence of heart failure, diabetes and abnormal glucose regulation increased with age. Body mass index and cholesterol were predictive factors for all three conditions in a multivariable model adjusting for cardiovascular risk factors and ischaemic heart disease. Moreover there was a linear association between increasing fasting glucose and incident abnormal glucose regulation or diabetes as well as heart failure. There was a strong association between abnormal glucose regulation and heart failure (Hazard Ratio 1.8, Cl: 1.52.3) and between diabetes and heart failure (HR 3.0, Cl: 2.3-4.0). Abnormal glucose regulation, diabetes and heart failure were linked to an unfavorable vital prognosis even after adjustment for cardiovascular risk factors and ischaemic heart disease. The trend towards an unfavorable prognosis of the combination of glucometabolic perturbations and heart failure did, however, not reach statistical significance compared to the prognostic information by each of these conditions on their own. Studies IV- V The feasibility and safety of the administration of recombinant Glucagon Like Peptide-1 (rGLP-1) was studied in a pilot investigation in six patients with type 2 diabetes and heart failure of ischaemic origin. A continuous subcutaneous infusion of rGLP-1 was administered during three days. Blood samples, 2-dimensional echocardiograms including Tissue Doppler imaging and exercise tests were obtained prior to and at the end of the infusion. The pilot study demonstrated the safety and feasibility of rGLP-1 and indicated that favourable effects may be achieved as regards left ventricular function. The metabolic modulator trimetazidine or placebo was added to conventional treatment in twenty patients with type 2 diabetes and heart failure of ischaemic origin in a double blind cross over study design. Trimetazidine improved left ventricular ejection fraction somewhat but there were no significant differences in myocardial tissue function measured by Tissue Doppler imaging. Conclusion The prevalence and incidence of glucose abnormalities and heart failure increases with increasing age. The prevalence of heart failure increases with worsening level of glucose abnormality. Glucose levels predict the occurrence of heart failure and there is a strong association between glucose abnormalities and heart failure. Recombinant GLP- 1 and trimetazidine seem to be safe to use in patients with ischaemic heart failure and diabetes. They did not improve the myocardial function significantly and further studies are needed before these metabolic modulators can be recommended in this patient group.