Cardiology Express Report™

Publication date: 2007-04-16

Defining and Addressing Residual Cardiovascular Risk

0.5 AMA PRA Category 1 Credit^TM available online at www.millennium-cme.com/go/lipid-disorders

This report was reviewed for medical and scientific accuracy by Sidney Alexander, MD, Director Lipid Clinic, Chairman Emeritus Cardiovascular Division, Lahey Clinic Medical Center, Burlington, Massachusetts.

Expert Commentary

Only this section of the report was written by Sergio Fazio, MD, PhD, Division of Cardiovascular Medicine, Department of Medicine,

In recent years, significant progress has been made in identifying the risk factors associated with cardiovascular disease. Effective strategies for controlling the factors that contribute to coronary heart disease, stroke, and hypertension have been developed. But despite these advances, mortality from cardiovascular disease continues to increase worldwide. Of particular concern, the increasing prevalence of obesity is paving the way for an epidemic of diabetes and its subsequent increased risk of cardiovascular diseases. Indeed, by the year 2020, cardiovascular disease will surpass infectious and communicable diseases as a reason for loss of productive life years worldwide.¹

Although we possess potent and effective treatment options for controlling hypertension and hyperlipidemia, most of the expected cardiovascular events in populations with different degrees of cardiovascular risk have not been prevented. For example, there is a large body of evidence indicating that statin therapy, which effectively reduces low-density lipoprotein (LDL)-cholesterol, lowers hospitalization, days of lost work, and morbidity and mortality rates from cardiovascular disease. Despite these encouraging data, approximately two-thirds of all cardiovascular events still occur with statin therapy. ^2-7 This means that subjects at risk may benefit from additional therapies aimed at different targets. It is this “residual risk” of cardiovascular disease that we must effectively address if we are to reduce the clinical and economic burden imposed by cardiovascular disease.

According to current National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) guidelines, once target LDL-cholesterol goals (high risk <100 mg/dL; optional goal <70 mg/dL) have been achieved with statins, consideration should be given to fibrate or niacin therapy to optimize triglyceride and HDL-cholesterol levels. ⁸ This is critically important in patients with diabetes. Patients with diabetes or metabolic syndrome often present with atherogenic dyslipidemia characterized by elevated triglycerides, low HDL-cholesterol, and a preponderance of small dense LDL particles. ^9-11 This atherogenic dyslipidemia significantly correlates with the prevalence of coronary atherosclerosis and is significantly predictive of adverse vascular events. ¹¹ Therefore, in addition to vigorous lowering of LDL-cholesterol, reducing triglycerides and increasing HDL-cholesterol should be considered important aspects of lipid management in patients with diabetes. ^11,12 Fibrate therapy reduces triglycerides by 20% to 50%, increases HDL-cholesterol by 10% to 35%, and may also reduce the number of small dense, highly atherogenic LDL particles. ⁸ Statin therapy may increase HDL-cholesterol by 5% to 15% and reduce triglycerides by 10% to 30%.¹³ Numerous studies show that a combination of fibrate and statin improves the lipid profile compared to statin use alone.

This Cardiology Express Report^TM reviews the concept of residual risk and potential management strategies to effect its reduction.

Residual Risk of Cardiovascular Disease

Lipid management has typically focused on control of LDL-cholesterol. Statin therapy has been the cornerstone of cardiovascular risk management due to the large number of patients at different levels of risk who have shown significant cardiovascular event reduction. In clinical t