Diabetes mellitus in patients with coronary artery disease : cardiovascular risk assessment and impact of available treatments

Abstract

A majority of patients with coronary artery disease have abnormal glucose regulation and as many as 30% overt diabetes mellitus. Despite considerable improvements in the management of cardiovascular diseases, patients with diabetes have not benefited to the same extent as those without this disease. Possible explanations are poor glycaemic control and inferior efficacy or insufficient use of available treatments in these patients.

Aims: 1. To investigate diagnostic and therapeutic strategies in patients with coronary artery disease by diabetic state; 2. To assess clinical practice in relation to existing guidelines; 3. To compare the impact of evidence-based medications and revascularisation procedures on mortality and major cardiovascular events in patients with coronary artery disease with and without diabetes mellitus; 4. To describe glucose lowering therapy in relation to cardiovascular prognosis; 5. To, at an early stage, identify coronary artery disease patients at a high risk of future cardiovascular events.

Management of coronary artery disease: Diabetes mellitus was reported in 1,524 (31%) of 4,961 patients enrolled, all with coronary artery disease. Among the 1,872 patients with acute coronary syndromes the diabetic status did not influence the propensity to use different pharmacological agents (except renin-angiotensin-aldosteron system blockers; odds ratio 1.33, p = 0.03) or coronary interventions. In patients with stable coronary artery disease (n = 2,854) secondary prevention guidelines were poorly adhered to: only 30% achieved blood pressure targets (< 140/90 mmHg) and lipid control was adequate in a minority of diabetic and non-diabetic patients (total cholesterol below 5 mmol/L: 55 versus 47%; LDL cholesterol below 3 mmol/L: 57 versus 51%).

Implementation of available tools: Of the eligible patients 44% and 43% of those with and without diabetes received evidence-based medications while 34% and 40% were revascularised. The use of evidence-based medications or of revascularisation in patients with diabetes mellitus provided an independent protective effect on one year mortality (HR 0.37, 95%CI 0.20-0.67; p = 0.001 and 0.72, 95%CI 0.39-1.32; p = 0.275) and cardiovascular events (HR 0.61, 95%CI 0.40- 0.91; p = 0.015 and 0.61, 95%CI 0.39-0.95; p = 0.025 respectively) compared to the effects that these two approaches produced in the non-diabetic patients.

Glucose lowering treatment: Out of 1,425 patients with known diabetes mellitus 378 were on insulin and 675 on oral glucose lowering drugs only. Insulin treated patients had an adjusted one year hazard ratio for mortality of 2.23 (95% CI 1.24-4.03; p = 0.006) and for cardiovascular events of 1.27 (95% CI 0.85-1.87; p = 0.230) compared to those on oral glucose lowering drugs. Within the 452 patients with newly detected diabetes 77 (17%) were started on glucose lowering drugs. None of them died compared to 25 (p = 0.002) among those without such treatment and their one year cardiovascular event hazard ratio was 0.22 (95% CI 0.05-0.97; p = 0.041) compared to untreated patients.

Predicting cardiovascular events: Based on easily available clinical variables (fasting plasma glucose, high density lipoprotein-cholesterol, and age) a single hidden layer Artificial Neural Network model reached a cross-validated misclassification rate of 37.8% compared to the glucose tolerance profile assessed by an oral glucose tolerance test. By the artificial network criterion1,283 patients with complete one year follow-up concerning cardiovascular events were divided in low and high risk groups within which the events were respectively 5.0 and 10.3% (p = 0.005). Adjusting for confounding variables patients in the high risk group had a one year cardiovascular event hazard ratio of 2.11 (95% CI 1.21- 3.67) compared to 1.37 (95% CI 0.79-2.36) for those assessed as diabetic by the oral glucose tolerance test.

Conclusions: European patients with diabetes mellitus admitted for acute coronary syndromes receive, when taking into account baseline characteristics, a comparable acute in-hospital management to their non diabetic counterparts. Secondary prevention of coronary artery disease is unsatisfactory both in patients with and without diabetes. Patients with diabetes benefit to a great extent from evidence-based medications or revascularisation procedures and the choice of glucose lowering modality seems prognostically important. Early institution of glucose lowering drugs seems beneficial in patients with newly detected diabetes mellitus. The Artificial Neural Network criterion, based on easily available clinical variables, has shown interesting risk stratification capacities.