Diabetes mellitus, glucose abnormalities and acute coronary syndromes : studies on prevalence, risk and impact of treatment

Sammanfattning: Background: Persons with diabetes mellitus and impaired glucose tolerance are at increased risk for cardiovascular disease.The prevalence of known diabetes among patients with acute myocardial infarction, about 20%, is expected to increase in the coming decades. Despite recent improvements in the overall management of cardiovascular disease, the mortality after myocardial infarction in patients with diabetes remains high. Aims: This thesis analyses the relation between glucose abnormalities and acute coronary syndromes focus on: 1. Risk factors and the importance of insulin based meticulous metabolic control in patients with diabetes and acute myocardial infarction; 2. The actual prevalence of glucose abnormalities in patients with acute myocardial infarction; 3. The use of evidenced based treatment in patients with diabetes and acute myocardial infarction; 4. The effect of early revascularisation in patients with diabetes and with unstable coronary artery disease. Blood glucose as a risk factor: In the prospective randomised DIGAMI study including 620 patients with acute myocardial infarction, insulin-based intense metabolic care initiated by a 24 hours insulin-glucose infusion followed by at least three months of subcutaneous multidose insulin treatment, reduced the long-term mortality with almost 30%. The most important risk factors for long-term mortality were high age, previous heart failure, and the glucometabolic state at admission. Besides established risk factors poor metabolic control at admission indicated a worse prognosis, which was attenuated by intense insulin treatment. Plasma glucose was examined at admission in 197 patients with acute myocardial infarction without previously known diabetes mellitus. During two years of follow up 40% had a major cardiovascular event. Independent risk factors for such event were a high admission plasma glucose, previous heart failure and high age. Thus, even among non-diabetic patients with acute myocardial infarction a high glucose level at admission identifies patients with worse prognosis. Glucose abnormalities and acute coronary syndromes: In 181 non-diabetic patients with acute myocardial infarction, who were examined with oral glucose tolerance tests during their initial hospitalisation, 3 1% fulfilled established criteria for diabetes mellitus while 35% had impaired glucose tolerance. These proportions were similar three months later, 25% and 40% respectively. Thus, previously undetected diabetes mellitus and pre diabetes were surprisingly common. Diabetes and acute coronary syndromes: In RIKS-HIA, (Swedish Register of Information and Knowledge about Swedish Care Units) the mean prevalence of diabetes was 20% among 25 632 persons below the age of 80 years who were hospitalised 1995-98 with an acute myocardial infarction. Diabetes was a strong independent predictor for mortality during the first year. Evidenced based treatment was similarly efficacious in patients with and without diabetes, however, significantly less utilised in the diabetic cohort. Thus, there are potentials to improve the prognosis of diabetic patients with myocardial infarction simply by better use of standard treatment. In the FRISC 2 trial, on the effect of early revascularisation in patients with unstable coronary artery disease, 299 (12%) of the patients had a previously diagnosed diabetes mellitus. The primary endpoint, death or a non-fatal reinfarction during one year of follow up was more prevalent among patients with diabetes. The relative improvement in prognosis induced by early revascularisation was similar in both groups. After adjustment for risk factors including number of diseased coronary arteries, diabetes remained as the strongest predictor for an unfavourable outcome. Thus, factors beyond the extent of coronary artery atherosclerosis seems to be of importance for the outcome in patients with diabetes mellitus and unstable coronary artery disease. Conclusions: Diabetes and pre-diabetes are considerably more common among patients with acute myocardial infarction than previously expected. Diabetic patient still have a worse outcome following an acute coronary event. Meticulous insulin-based metabolic care and a proper use of existing evidence-based treatment and when suited, early revascularisation, will improve the prognosis. It can be assumed that improved awareness of the glucometabolic condition among patients with acute coronary events may open for new secondary preventive treatment strategies in this patient category.