The US Food and Drug Administration (FDA) gave clearance to market the Albumin Cobalt Binding (ACB) test for detection of Ischemia Modified Albumin (IMA) in February 2003. IMA is a serum biomarker that can be used as an aid to the early evaluation of acute coronary syndromes (ACS) prior to heart attack in patients presenting with chest pain suggestive of cardiac origin. The ACB test uses a small amount of blood drawn from a patient, which is then run on a chemistry instrument commonly available in hospital laboratories.

IMA was first identified by an emergency physician seeking a rapid, reliable blood test for ischemia. Differences in blood samples between apparently healthy volunteers and ischemic patients were found to be due to changes in albumin, the most common protein in blood. IMA is produced when albumin circulating in blood comes in contact with ischemic tissue in the heart or other organ. During ischemia, a series of chemical reactions occur that modify albumin, resulting in Ischemia Modified Albumin. IMA is produced continually during ischemia, which means IMA levels in blood change quickly. Patients at low risk for ACS have proportionately less IMA than patients at high risk or with confirmed ACS.

Only about one in five patients with chest pain are ultimately diagnosed with ACS. The challenge therefore is to determine which patients have ACS, and which can be safely discharged home. Currently available tests such as electrocardiography (ECG) and other biomarkers such as troponin are limited in their impact on making "rule-out" decisions. This decision process often takes from 8 to 24 hours. About 75 percent of patients are in a "grey zone", in which the emergency physician must weigh the trade-offs of accelerating treatment versus "watchful waiting" and additional diagnostic testing. In this case, IMA may assist emergency physicians to "rule out" ACS in low risk patients. With IMA, up to 40 percent of chest pain patients could be safely discharged within a few hours.

"The availability of a new, highly sensitive, serum marker for myocardial ischemia will have significant impact on clinical practice in the emergency department," stated Charles Pollack, MD, chairman of the emergency department at Pennsylvania Hospital and associate professor at the University of Pennsylvania, and a clinical investigator of IMA.

"For several years, the clinical community has been looking for a reliable, inexpensive test to determine which chest pain patients can be sent home safely," explained Robert Jesse, MD, PhD, associate professor of cardiology at the Medical College of Virginia, which was one of twenty research sites involved in clinical studies of IMA. "Studies showed that IMA, when used in conjunction with ECG and troponin, correctly identified low-risk patients who could be discharged safely using test results from patient presentation, without the need for more extensive testing in the ED."

The emergency physician currently has three diagnostic tools available at the time a patient presents to help assess the likelihood of ACS: 1) ECG; 2) biomarkers of cardiac necrosis (troponin, CKMB, myoglobin), and 3) history and physical examination. Using these tools at patient presentation, the emergency physician can typically diagnose 12 percent of patients based on diagnostic ECG or elevated markers of necrosis. Another 13 percent can be considered for discharge based on history and physical findings. IMA adds a fourth diagnostic tool, which helps to confirm the chances of ACS in low risk patients.

Losartan reduces urinary albumin excretion in normotensive type 2 diabetics, according to the results of a randomized trial published in the July 15, 2003 issue of the Annals of Internal Medicine. This is the first study of an angiotensin-receptor antagonist in normotensive patients.

"Angiotensin-converting enzyme (ACE) inhibitors reduce albumin excretion in both normotensive and hypertensive patients with type 1 or type 2 diabetes," express Adrienne A. M. Zandbergen, MD, from Ikazia Hospital in Rotterdam, the Netherlands, and colleagues. "Because reduction in microalbuminuria is associated with marked renal protection, the delay or retardation of the disease process is important in the management of diabetes mellitus."

In this multicentre, double-blind trial, 147 patients with type 2 diabetes mellitus and microalbuminuria were randomized to receive losartan 50 mg daily for five weeks followed by 100 mg daily for five weeks, or 10 weeks of placebo.

The losartan group had a significant 25% reduction in albumin excretion rate after five weeks on 50 mg daily, with a further reduction (34%) over the next five weeks on 100 mg daily (Figure 1). In contrast, in patients receiving placebo, there was a slight reduction in albumin excretion rate at 5 weeks whereas at the end of ten weeks there was an increase in albumin excretion rate by 10.3%. Blood pressure decreased slightly, and adverse effects were similar to those in the placebo group. Multivariate analysis revealed that the antiproteinuric effect of losartan was independent of blood pressure reduction. When losartan was discontinued, albumin excretion rate returned to pretreatment baseline levels.

The authors concluded that losartan reduces urinary albumin excretion in normotensive patients with type 2 diabetes mellitus and microalbuminuria.

Sibutramine is a potentially valuable adjunct to metformin treatment in appropriately selected obese type 2 diabetic patients and it improves metabolic control in individuals who lose >5% weight, as reported in the January 2003 issue of Diabetes Care.

"Management of type 2 diabetes often fails to meet the stringent treatment targets for glycemia, lipids, blood pressure, and other cardiovascular risk factors. The importance of obesity as a determinant of cardiovascular outcome has generally been neglected, despite accumulating evidence that it plays a crucial role," noted the researchers.

This 12-month study was conducted at 21 primary and secondary care centers in England, France, Canada and Belgium by the Multicentre Sibutramine Study Group investigators, Dr. McNulty SJ and his colleagues. It involved 195 patients with type 2 diabetes and a body mass index (BMI) >27 kg/m2. All the patients were on metformin treatment and further randomized to sibutramine 15 mg/day or sibutramine 20 mg/day or placebo. Patients with ischemic heart disease, heart failure or stroke were excluded. Metformin dosage was adjusted if necessary, but other antidiabetic drugs were not used.

The results revealed that at the end of one year, sibutramine induced significant weight loss with both 15 mg/day (5.5 0.6 kg) and 20 mg/day (8.0 0.9 kg), whereas placebo did not (0.2 0.5 kg). Weight loss > 10% was achieved by 14 and 27% of subjects receiving 15 and 20 mg, respectively, but by none given placebo (Figure 1). Glycemic control improved in parallel with weight loss, and subjects who lost >10% weight showed significant decreases in both HbA1C (1.2 0.4%, P<0.0001) and fasting plasma glucose (1.8 mmol/l, P<0.001). HDL cholesterol increased slightly with the higher dose, whereas plasma triglycerides fell with both doses, especially in subjects with weight loss of > 10% (a 29% decrease, P<0.01).

Weight loss of > 10% confers important metabolic and cardiovascular benefits in obese type 2 diabetic patients. The researchers concluded that "sibutramine can be an effective adjunct to metformin treatment in selected obese type 2 diabetic subjects and improves metabolic control in individuals who lose weight."

Ramipril produces a mild reduction in levels of advanced glycation end products, perhaps reflecting decreased oxidative stress, in patients with mild-to-moderate non-diabetic nephropathy as reported in the April 2003 issue of Journal of Human Hypertension.

Researchers from the Institute of Preventive and Clinical Medicine and the Military Hospital, Bratislava, Slovakia, as well as the University Wuerzburg, Germany, enrolled 12 patients with newly diagnosed mild-to-moderate non-diabetic nephropathy, who received ramipril (2.5-5 mg) for two months and data was compared with a group of non-diabetic nephropathy patients taking diuretics and beta-blockers and with age- and sex-matched healthy controls.

In this study, as compared to controls, patients with non-diabetic nephropathy showed higher levels of advanced glycation end products, carboxymethyllysine, advanced oxidation protein products, lipofuscin and homocysteine as well as mild-to-moderate renal insufficiency.

Ramipril reduced blood pressure and proteinuria, while creatinine clearance did not alter. Ramipril also mildly decreased levels of advanced glycation end products (AGE), while concentrations of advanced oxidation protein products (AOPP) and malondialdehyde declined.

This offers the first evidence that ramipril reduces levels of advanced glycation end products. The decline in advanced oxidation protein products and malondialdehyde suggests a reduction in oxidative stress. Conventional treatment with diuretics and beta-blockers did not significantly alter these parameters.