Causes and mechanisms of an adverse outcome in patients with glucose abnormalities and cardiovascular disease : epidemiological and biochemical analyses

Sammanfattning: Background: Diabetes and previously undetected glucose abnormalities are common in patients with acute myocardial infarction (AMI). It is well established that patients with diabetes have a higher mortality rate after coronary events than patients without diabetes but the complication pattern in a contemporary perspective, the impact of glucose control and whether unknown glucose abnormalities affect the longterm prognosis is less well studied. Data on the prognostic implications of adipokines in patients with prevalent coronary heart disease are contradictory and long-term outcome studies are lacking. Aims: To identify high-risk individuals and study long-term prognosis by 1. Investigating the lasting effect of intensified, insulin-based glucose control on mortality after AMI in patients with diabetes. 2. Analysing mortality and morbidity patterns after AMI in patients with newly discovered glucose abnormalities. 3. Investigating complication patterns after a first percutaneous coronary intervention. 4. Analysing the significance of adiponectin and leptin as biomarkers of cardiovascular complications. Glucose control and mortality after AMI: 306 patients with AMI and diabetes were randomised to intensified insulin-based glycaemic control while 314 served as controls in the DIGAMI-study. During a mean follow-up of 7.3 years 90% of the study population died. The median survival was 2.3 years longer in patients receiving intensified insulin-based glycaemic control after AMI (7.0 years) compared to patients in the control group (4.7 years). Impact of undetected glucose abnormalities on long-term outcome after AMI: Patients (n=167) with AMI and healthy controls (n=184) without previously known diabetes (included in the GAMI study) were investigated with an oral glucose tolerance test (OGTT) at the time of hospital discharge (patients) or at inclusion (controls). Cardiovascular events (cardiovascular mortality, AMI, heart failure and stroke) during 10 years of follow-up were more frequent in patients with abnormal glucose tolerance than in patients with normal glucose tolerance and in controls. Abnormal glucose tolerance at the OGTT was independently associated with future cardiovascular events after an AMI (HR 2.30; 95% CI 1.24-4.25, p=0.008) in contrast to HbA1c (p=0.81) and fasting blood glucose (p=0.52). Long-term outcome after coronary artery disease and revascularisation: High event rates of mortality, heart failure, myocardial infarction and stroke were demonstrated after a first percutaneous coronary intervention in patients with diabetes followed up to five years after inclusion in the Swedish Coronary Angiography Angioplasty Registry (SCAAR) between 2006-2010 (n=58891, 19% with diabetes). Diabetes was an independent predictor for mortality and cardiovascular events. Insulin-treated patients were at a particularly high risk. Adiponectin and leptin as biomarkers for identifying high risk patients: In 180 patients with AMI and without diabetes (the GAMI cohort) elevated levels of adiponectin at discharge independently predicted mortality (HR 1.79; 95% CI 1.07-3.00, p=0.027) but not cardiovascular events the coming decade. High levels of leptin at day 2 were associated with cardiovascular events during the first seven years but did not predict mortality. Conclusion: Diabetes and previously undetected glucose abnormalities are common in patients with coronary events and their presence has a negative influence on the prognosis. Despite improved longevity patients with diabetes are still at increased risk for mortality and cardiovascular complications. An OGTT, but not HbA1c, identifies patients with previously undetected glucose abnormalities at increased cardiovascular risk the next coming 10 years. These findings support that an OGTT should be considered as an important screening tool after AMI. High levels of adiponectin and leptin identifies patients with compromised outcome after AMI. Future studies are warranted to confirm their role as suitable biomarkers. Finally a close follow-up of patients with glucose abnormalities is advocated where multifactorial treatment is important to improve long-term survival after AMI. The present studies do also underline that new treatment strategies are highly warranted.