CARDIOLOGY EXPRESS REPORT

Publication date: 2007-05-01

Triglycerides and HDL-cholesterol: Targeting Independent Risk Factors That Contribute to 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

Provided by

Dean A. Bramlet, MD, FACC, FACP, FAHA, Diplomat of Clinical Lipidology; Medical Director and Founder, The Heart and Lipid Institute of Florida, Tampa - St. Petersburg, Florida; Adjunct Faculty, Department of Community Health and Family Medicine, The University of Florida Health System, Gainesville, Florida; Assistant Consulting Professor of Medicine, Duke University, Durham, North Carolina

Despite the development of potent and efficacious treatment options for recognized risk factors associated with cardiovascular disease (eg, diabetes, hypertension, hyperlipidemia), the majority of adverse cardiovascular events still occur. It is well established that statin therapy effectively reduces low-density lipoprotein (LDL)-cholesterol and lowers morbidity and mortality associated with cardiovascular disease. These same data, however, indicate that approximately two-thirds of all adverse cardiovascular events are not prevented with statin therapy.^1-6

There is evidence to suggest that lipid abnormalities other than LDL-cholesterol, such as elevated triglycerides and low high-density lipoprotein (HDL)-cholesterol, contribute to this “residual risk” of cardiovascular disease.^7-13

A meta-analysis of 17 prospective studies of triglyceride and cardiovascular disease found statistically significant increases in cardiovascular disease risk associated with increased triglyceride levels.¹¹ An increase of 1 mmol/L (89 mg/dL) in triglycerides was associated with a 32% increase in the risk of cardiovascular disease in men (relative risk 1.32, 95% Confidence Interval [CI], 1.26-1.39) and a 76% increase in women (relative risk 1.76, 95% CI, 1.50-2.07).¹¹ In the Prospective Cardiovascular Munster (PROCAM) study,8 the greatest incidence of coronary heart disease was found in male patients characterized by both elevated triglyceride levels (>204 mg/dL) and reduced HDL-cholesterol levels (<35 mg/dL). An 8-year follow-up study of PROCAM revealed a significant and independent association between serum triglyceride levels and the incidence of major coronary events.¹⁰ When elevated triglycerides (>200 mg/dL) coincided with a high ratio of LDL-cholesterol to HDL-cholesterol (>5), the risk of coronary heart disease was elevated 6-fold. ¹⁰ In the Helsinki Heart Study (HHS), ¹² patients characterized by both triglyceride levels >204 mg/dL and by HDL-cholesterol levels <42 mg/dL had an 81% higher relative risk of cardiovascular events. In a study of approximately 13,000 patients with established coronary heart disease, HDL-cholesterol and triglycerides were significantly strong predictors of recurrent coronary events in patients with LDL-cholesterol levels <125 mg/dL. ¹³ For a 10 mg/dL increase in triglycerides, the coronary event rate increased by 2.5% in patients with LDL-cholesterol levels <125 mg/dL, while a 10 mg/dL increase in HDL-cholesterol decreased the coronary event rate by 29%.¹³

The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) guidelines state that once target LDL-cholesterol goals have been achieved with statins, fibrate (fenofibrate, gemfibrozil) or niacin therapy should be considered to optimize triglyceride and HDL-cholesterol levels. ¹⁴ Fibrate therapy typically reduces triglycerides by 20% to 50% and may increase HDL-cholesterol levels up to 10% to 20%;^15,16 whereas statins variably increase HDL-cholesterol 5% to 15% and reduces triglycerides by 10% to 30% in a dose-dependent manner. ¹⁵ Extended-release niacin therapy has