Trimetazidine therapy might improve left ventricular function when combined with standard anti-anginal therapy in patients with type 2 diabetes and ischaemic cardiomyopathy, as per a study published in November 2003 issue of Cardiovascular Diabetology.

Patients with diabetic cardiomyopathy have an impaired myocardial glucose handling and distal distribution of coronary atherosclerosis. Until recently, haemodynamic agents have been the only treatment available for patients with angina. Metabolic agents, such as trimetazidine, are a new therapeutic approach that directly modifies the use of energy substrates in the heart, reducing ischaemic injury and improving cardiac performance during ischaemia.

Giuseppe M.C. Rosano, Tosinvest Sanità San Raffaele, Rome , Italy , and colleagues performed a study to evaluate the effect of trimetazidine on left ventricular function (LVF) in diabetic patients with coronary artery disease. They enrolled 32 patients with type 2 diabetes and a mean age of 65.4 years, all with chronic stable angina and LVF below 50%. Patients were randomized to 6 months of treatment with either thrice daily trimetazidine 20 mg or matching placebo. Additional routine therapies used for the treatment of myocardial ischaemia and heart failure were continued during the study period. The researchers evaluated LVF by transthoracic echocardiogram at baseline and at 6 months.

The results showed that trimetazidine significantly decreased left ventricular end diastolic and systolic diameters (63.2 to 58 mm and 41.1 to 34 mm, respectively, p  < 0.05 for both), whereas no significant changes were detected in the placebo group (Figure 1). The trimetazidine group showed an improvement in left ventricular ejection fraction of 5.4% while placebo group had a decrease of 2.4% ( p  < 0.01). Trimetazidine also significantly decreased the wall motion score index (from 1.37 + 0.2 to 1.26  +  0.16, p < 0.01) while it remained unchanged in patients treated with placebo (from 1.38 + 0.3 to 1.42 + 0.21). Further, trimetazidine significantly improved left ventricular diastolic function evaluated through E/A on mitral flow (from 0.68 + 0.1 to 0.89 + 0.3) while it remained unchanged in placebo.

“Adjunct therapy of trimetazidine to standard anti-anginal therapy improves left ventricular systolic and diastolic function of chronically dysfunctional myocardium in patients with type 2 diabetes, coronary artery disease and depressed left ventricular function,” the researchers concluded, suggesting that the adjunct of targeted cardiac metabolic therapy to usual care improves areas of hibernated myocardium.

Improvements are seen in platelet, endothelial and haemorrheological function when high-risk hypertensive patients are under intensive blood pressure control and cardiovascular risk management, according to a prospective, follow-up substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) published in the January 2004 issue of Journal of Internal Medicine.

Effective control of blood pressure levels through antihypertensive therapy does not reduce cardiovascular risk to that of the normotensive population. The total cardiovascular risk profile must be considered in order to prevent cardiovascular complications. Various markers of endothelial and platelet function, as well as haemorrheological indices, are also significant cardiovascular risk factors. However, little is known regarding how anti-hypertensive therapy affects these markers.

Charles GC Spencer, MBBS, MRCP, and colleagues at the City Hospital , Birmingham , United Kingdom , investigated the impact of intensified blood pressure control and cardiovascular risk factor management on platelet, endothelial and haemorrheological function in hypertensive patients at high risk of coronary artery disease. This prospective follow-up study included 159 hypertensive patients and 80 age and sex-matched healthy controls. Hypertensive patients received intensive antihypertensive therapy towards a goal of < 140 mmHg systolic blood pressure (SBP) and < 90 mmHg diastolic blood pressure (DBP). Markers of platelet, endothelial and haemorrheological function were assessed at baseline and 6 months after treatment.

Significant decreases in mean SBP and DBP ( p  < 0.0001) and in mean serum cholesterol levels were observed ( p  < 0.0001). However, there was no change in HDL cholesterol levels. A significant reduction in mean haematocrit, mean white blood cell count (WBC) and median plasma viscosity was also found. The authors highlighted that these are “indicators of adverse cardiovascular prognosis” and “their reduction would therefore be expected to contribute to an overall reduction in cardiovascular risk.” Surprisingly though, treatment did not significantly affect other haemorrheological indices, including fibrinogen levels or platelet count. Improvement was also seen in a marker of platelet function and a marker of endothelial damage and dysfunction.

Notably, similar trends were observed in a subgroup of 65 patients who did not receive statins during the study. Further analysis revealed that patients who showed the greatest response to treatment were more likely to have been previously untreated and had higher SBP, DBP and serum total cholesterol levels at baseline. Responders also had a higher WBC and platelet count at baseline as compared to nonresponders. Moreover, younger patients and those with higher platelet counts were more likely to achieve excellent blood pressure control.

The authors concluded that, “intensified cardiovascular risk management results in significant improvements in indices of endothelial, platelet and rheological function in a hypertensive population at high risk of cardiovascular events. These improvements appear to be independent of the degree of change in BP. Given the fundamental role of interactions between the endothelium and circulating blood components in the pathogenesis of hypertensive complications, this may be of importance in preventing adverse cardiovascular outcomes.”

The third European guidelines on cardiovascular disease (CVD) prevention, launched at this year's European Society of Cardiology (ESC) Congress, were published in December 2003 issue of the European Journal of Cardiovascular Prevention and Rehabilitation . The guidelines were influenced by the results of the second EUROpean Action on Secondary Prevention through Intervention to Reduce Events (EUROASPIRE II) survey, which was conducted in 15 European countries.

EUROASPIRE was part of a major ESC initiative promulgated to update and replace the Framingham database with a data set that is based on current European population demographics. Examination of these new data revealed that the management of patients' risk factors has not been effective in achieving the goals for CVD prevention set out in the joint European societies' 1998 guidelines. As a result, the new guidelines differ in several major aspects from the previous ESC guidelines, which were largely based on data from the Framingham Heart Study.

These guidelines have abandoned the Framingham model and are based on this new, large European database of almost 3 million person-years of observation followed for almost 10 years with > 7000 fatal cardiovascular events as an endpoint.

The guidelines were prepared by Third Joint European Societies' Task Force on Prevention of Cardiovascular Disease, chaired by Guy G De Backer, MD ( Ghent University Hospital , Belgium ).

The objectives of the guidelines are to reduce the incidence of first or recurrent clinical events due to coronary heart disease, ischemic stroke, and peripheral artery disease. The focus is prevention of disability and early death. To this end, the guidelines address the role of lifestyle changes, the management of major cardiovascular risk factors, and the use of different prophylactic drug therapies.

Newer Aspects of the Guidelines

l The guidelines are concerned with the prevention of CVD rather than just coronary heart disease (CHD). The etiologies of myocardial infarction, ischemic stroke and peripheral arterial disease are similar, and recent intervention trials have shown that several forms of therapy prevent not only coronary events and revascularizations, but also ischemic stroke and peripheral artery disease. Hence, initiation of specific preventive action is recommended based on estimation of risk of any vascular event.

l The risk assessment uses the Systemic COronary Risk Evaluation (SCORE) model and risk charts, which can be adapted to different national conditions, resources, and priorities, and takes into account the heterogeneity in CVD mortality across European populations.

l Risk is defined in terms of the absolute 10-year probability of developing a fatal rather than any cardiovascular event.

l The threshold for high risk of a fatal cardiovascular event is now defined as > 5% rather than > 20% as previously.

l The first priorities in clinical practice are patients with established CVD, peripheral artery disease or cerebrovascular lesions; asymptomatic individuals at high risk for developing atherosclerotic CVD; and close relatives of both groups.

l Updated recommendations are given regarding behavioral changes, risk factor management and the prophylactic use of drugs.

The guidelines recommend that in patients at potentially high risk of CVD, the risk of total CVD should be assessed by the SCORE system. Goals in these patients and those with established CVD should be lifestyle modification and control of risk factors: blood pressure (<140/90 mmHg in most, <130/80 mmHg in some), total cholesterol (150 mg/dL in most, 175 mg/dL in some), LDL cholesterol (115 mg/dL in most, 100 mg/dL in some) and good glycemic control in all persons with diabetes.

A new European risk prediction system, SCORE, has been developed to define the lifestyle, risk factor, and therapeutic targets for CVD prevention. SCORE is representative of typical European populations, and the risk score system has been optimized for coronary prevention in European clinical practice.

The SCORE system differs from the European task force chart used in previous guidelines in important ways (Table). SCORE was developed using data from 12 European cohort studies (N = 205,178), some with multiple component cohorts, mainly population studies covering a wide geographic spread of countries at different levels of cardiovascular risk. The SCORE data comes from one quarter million persons and contains some 3 million person-years of observation and more than 7000 fatal cardiovascular events. It addresses fatal events rather than total events, total cardiovascular risk rather than just CHD, charts for cholesterol and cholesterol:HDL ratio and includes more detail for the 50- to 65-year age range. No charts are included for individuals with established disease or diabetes.

Table. ESC Task Force Chart (1998) Compared With the SCORE System (2003)

Task Force Chart	SCORE System
Based on 5000 American individuals	Based on > 200,000 Europeans at different levels of CV risk
Predicts “coronary event”	Predicts CVD
Uses idiosyncratic definition	Uses common definition
Includes nonfatal events	Restricted to fatal events
Cannot be adjusted using national mortality data	Can be customized using national mortality statistics

Risk estimation is based on age, sex, smoking habits, systolic blood pressure (SBP) and either total cholesterol or cholesterol/HDL ratio. Using the SCORE model, risk charts can be provided for all European countries. Relative risk is calculated by comparing an individual's risk category with that of a nonsmoking person of the same age and gender with blood pressure <  140/90 mmHg and total cholesterol < 5 mmol/L (< 190 mg/dL).