Glucose regulation and coronary artery disease : studies on prevalence, recognition and prognostic implications

Coronary artery disease and diabetes mellitus type 2 represent chronic diseases of substantial and growing prevalence. Their coincidence is common, markedly enhancing mortality and morbidity. The risk for cardiovascular disease increases along a spectrum of blood glucose concentrations from levels regarded as normal. Therefore, strategies for the early detection of glucometabolic disturbances in patients with coronary artery disease are needed to better understand the impact on prognosis and improve treatment.

Aims: This thesis addresses glucose regulation in patients with coronary artery disease with the following specific aims: 1. To study glucose tolerance in patients with myocardial infarction and population-based controls; 2. To assess the prevalence of glucose regulation categories in patients with acute and stable coronary artery disease; 3. To compare the different diagnostic modalities for recognising abnormal glucose regulation; and 4. To investigate whether the glucometabolic state detected early after myocardial infarction relates to long-term prognosis.

Glucose tolerance in patients and population-based controls In a prospective study 181 patients without diabetes admitted for acute myocardial infarction were matched for age and gender with control individuals without cardiovascular disease recruited from the population registry. A standard 75-g oral glucose tolerance test revealed that 35% of 185 controls compared with 67% of 168 patients at hospital discharge and 66% of 145 three months later had abnormal glucose tolerance. Compared to controls dyslipidaemia and hypertension was more common among patients, who were further characterised by higher glycaemia, insulin resistance, triglycerides, fibrinogen, and proinsulin levels.

The prevalence of glucose regulation categories A total of 4 961 patients referred to a cardiologist due to coronary artery disease were recruited in 110 centres across Europe (acute admissions n=2 107; elective consultations n=2 854). Diabetes was already known in 1524 patients. From 3 437 of the remaining subjects, fasting glycaemia was available in 2 679 while 1 920 underwent an oral glucose tolerance test. Newly detected diabetes was recognised in 22 and 14% of patients with acute and elective manifestation of coronary artery disease. Impaired glucose tolerance was found in 32% of each group and impaired fasting glucose in further 4 and 5%. Thus, more than half of patients without already known diabetes had normal glucose regulation.

Recognition of patients with abnormal glucose regulation Glucometabolic status was assessed by means of fasting and 2-hour post load glycaemia in 1 867 patients with confirmed diagnosis of coronary artery disease without previously known diabetes or impaired glucose regulation. Among 591 patients with impaired glucose tolerance, 84% had fasting plasma glucose < 6.1 and 65% < 5.6 mmol/L. Out of 319 patients with newly detected diabetes 45% had fasting glycaemia < 6.1 and 29% < 5.6 mmoIL. If the glucometabolic state was classified by fasting glycaemia only, abnormal glucose regulation would have remained undetected in 48% (478) patients. The best algorithm to estimate abnormal glucose regulation was obtained by a neural network statistical model including fasting glucose, age and HDL-cholesterol. The model enabled a reduction of the number of glucose tolerance tests inevitable for appropriate classification by 25%.

Glucose tolerance as prognostic factor: During follow-up (median 34 months) of 168 patients with acute myocardial infarction, who had glucose tolerance assessed before hospital discharge, 31 experienced at least one major cardiovascular event (cardiovascular death, non-fatal stroke, recurrent myocardial infarction or severe heart failure). The probability of remaining free from cardiovascular events was significantly lower in patients with abnormal than those with normal glucose tolerance (p=0.002). Abnormal glucose tolerance (hazard ratio 4.18, 95% Cl 1.26-13.84, p=0.019) and prior myocardial infarction (hazard ratio 3.38, 95% Cl 1.627.04, p=0.001) were the strongest predictors of future events.

Conclusions: Abnormal glucose tolerance is almost twice as common among patients with a myocardial infarction as in population-based controls. Normal glucose regulation is less common than abnormal among patients with coronary artery disease. Abnormal glucose tolerance is a strong risk factor for future cardiovascular events after an acute myocardial infarction. An oral glucose tolerance test should therefore be a part of the evaluation of total risk in all patients with coronary artery disease. Since glucose disturbances are common and easy to detect they may be suitable targets for novel secondary preventive efforts.

List of scientific papers

I. Bartnik M, Malmberg K, Hamsten A, Efendic S, Norhammar A, Silveira A, Tenerz A, Ohrvik J, Ryden L (2004). Abnormal glucose tolerance--a common risk factor in patients with acute myocardial infarction in comparison with population-based controls. J Intern Med. 256(4): 288-97.
https://pubmed.ncbi.nlm.nih.gov/15367171

II. Bartnik M, Ryden L, Ferrari R, Malmberg K, Pyorala K, Simoons M, Standl E, Soler-Soler J, Ohrvik J; Euro Heart Survey Investigators (2004). The prevalence of abnormal glucose regulation in patients with coronary artery disease across Europe. The Euro Heart Survey on diabetes and the heart. Eur Heart J. 25(21): 1880-90.
https://pubmed.ncbi.nlm.nih.gov/15522466

III. Bartnik M, Ohvik J, Ryden L, Malmberg K, Pyorala K, Standl E, Ferrari R, Simoons ML, Soler-Soler J,on behalf of the Euro Heart Survey Investigators (2005). Identifying abnormal glucose regulation in patients with coronary artery disease. A report from the Euro Heart Survey on diabetes and the heart. [Manuscript]

IV. Bartnik M, Malmberg K, Norhammar A, Tenerz A, Ohrvik J, Ryden L (2004). Newly detected abnormal glucose tolerance: an important predictor of long-term outcome after myocardial infarction. Eur Heart J. 25(22): 1990-7.
https://pubmed.ncbi.nlm.nih.gov/15541834