The European Society of Cardiology
a Department of Cardiology, Malmö University Hospital, 205 02 Malmö, Sweden
b Department of Medicine, University College London Medical School, London, UK
* Correspondence: Dr. L.R. Erhardt, Department of Cardiology, Malmö University Hospital, 205 02 Malmö, Sweden. Tel.: +46 40 33 1941; fax: +46 40 33 7329 (E-mail: leif.erhardt{at}medforsk.mas.lu.se).
Introduction
Cardiovascular disease (CVD) involves a complex interplay of risk factors, many of which share common pathogenic mechanisms. Risk factors, such as dyslipidaemia, hypertension, hyperglycaemia and diabetes, tend to cluster in individuals, and have a synergistic effect on CVD risk. For example, risk is greater in patients with diabetes compared with patients without diabetes. As a result, the National Cholesterol Education Program Third Adult Treatment Panel has formally recognized metabolic syndrome as a secondary target of risk-reduction therapy, after the primary target of low-density lipoprotein cholesterol.
The papers in this supplement are from a symposium entitled 'New Approaches to Managing Multiple Risk Factors in Cardiovascular Disease', which was held at the XXV Annual Congress of the European Society of Cardiology, in Vienna, on 2 September 2003.
In the first paper, Professor John Betteridge highlights that macrovascular damage can occur in individuals at risk of, but prior to, the onset of diabetes. Therefore, while the treatment of CVD risk factors in patients with overt diabetes reduces the incidence of CVD death, early identification and treatment of patients at risk of diabetes is also essential for the primary prevention of CVD. Furthermore, individuals with the metabolic syndrome have an increased risk of CVD prior to the development of impaired glucose tolerance and diabetes, and patients with both the metabolic syndrome and diabetes are at greater risk of CVD death than patients with either diabetes or the metabolic syndrome alone. While reduction in elevated glucose levels can significantly reduce the risk of microvascular disease in patients with diabetes and/or the metabolic syndrome, it is not sufficient to significantly reduce the risk of macrovascular disease. Therefore, he argues that additional risk factors, including hypertension and dyslipidaemia, must also be targeted in patients with these disorders.
Atherosclerosis — the underlying cause of CVD — is an inflammatory response to endothelial injury. The pathogenic mechanisms shared by hypertension and dyslipidaemia include oxidative stress, smooth muscle cell migration/proliferation, plaque destabilization, stimulation of the renin-angiotensin system, and insulin resistance. In the second paper, Professor Andrei Sposito discusses emerging insights into hypertension and dyslipidaemia synergies, highlighting the importance of addressing the underlying mechanisms of damage caused by risk factors in individual patients.
In the final paper, Professor Björn Dahlöf reviews data from clinical trials that demonstrate the benefits of aggressive versus moderate therapy, and of targeting risk factors in special patient populations, for the reduction of CVD risk. Hypertension and hypercholesterolaemia frequently coexist, and so concurrent treatments are required for both disorders. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) has investigated the impact of combining the effects of antihypertensive therapy with a statin. The multi-centre, 2x2 factorial design, randomized trial has compared two blood pressure (BP)-lowering regimens in the antihypertensive arm, and double-blind statin versus placebo in a separate lipid-lowering arm (LLA). The objective of the LLA was to compare the effects of low-dose atorvastatin versus placebo for the combined end-point of nonfatal myocardial infarction and fatal coronary heart disease (CHD) in hypertensive patients with normal to mildly elevated cholesterol levels. The LLA is the first study to assess the benefits of lipid lowering in the primary prevention of CHD in well-controlled hypertensive patients who are not conventionally deemed dyslipidaemic. The LLA was terminated prematurely due to a highly significant benefit with atorvastatin versus placebo. The results from the antihypertensive arm of ASCOT are keenly awaited. It is anticipated that controlling both BP and dyslipidaemia may have a synergistic effect on reducing CVD mortality and morbidity.
The overall message from the symposium, and from the papers in this supplement, is that future treatment strategies should focus on addressing the global CV risk in each patient and not just individual risk factors.
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