J. David Schnatz, M.D.
Director, Lipid Education Service
Saint Francis Hospital and Medical Center
114 Woodland Street, Hartford, CT 06105
Telephone: (860) 714-5555

May 1999

The program of the 48th annual Scientific Session of the American College of Cardiology contained the following selected abstracts:

Abstract 1135-69 Is There a Benefit to Lowering Low/Density Lipoprotein Below 100 mg/dl in Patients with Coronary Artery Disease?

Endothelium dependent (ED) and endothelium independent (EI) brachial artery vasoreactivity (BRT) was assessed in 44 stable patients with coronary artery disease (36 men, 8 women, mean age 66), all of whom were on LDL lowering therapy. The mean LDL values of the two groups were 75 mg/dl and 106 mg/dl (p<0.0001). LDL lowering improved both the ED (p<0.03) and EI (p<0.05) vasoreactivity. The authors concluded that, "There may be additional benefit to lowering LDL-C < the current NCEP guidelines".

Abstract 1194-113 Massive Cholesterol Lowering Acutely Improves Myocardial Vascular Responsiveness in Familial Hypercholesterolemia

Six men and one woman with heteozygous familial hypercholesterolemia (FH), mean age 47, underwent lipoprotein apheresis for 6 to 24 months. All but one had coronary artery disease. A mean cholesterol of 297 mg/dl was reduced by 77%, an LDL of 221 by 91.5%, ApoB of 169 by 87%, HDL of 43 by 6%, triglyceride of 115 by 64%, and Lp(a) of 37 by 89%. Endothelial leukocyte adhesion molecule and soluble intercellular adhesion molecule were reduced significantly (p<0.003 and <0.0001, respectively). While myocardial blood flow at rest did not change with apheresis, after adenosine stimulation, it did increase significantly as a result of apheresis (p<0.05). The authors conclude that in FH patients " 'aggressive' LDL apheresis may be a useful tool to acutely reverse coronary vascular dysfunction".

Abstract 824-3 Predicting Risk of First Acute Major Coronary Events (AMCEs) in the Airforce/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS)

Six thousand six hundred five individuals without atherosclerotic disease (15% women) were treated with 20-40 mg of Lovastatin (Lov) vs placebo (Plc). The average LDL of 150 � 17 mg/dl decreased 25%, HDL of 37 � 6 mg/dl increased 6%, and the incidence of first AMCE's decreased 37% (p<0.001). Baseline HDL, LDL/HDL, Chol/HDL, apolipoprotein-A-1, apolipoprotein B and B/A-1 were significant predictors of AMCE. After 1 year of Rx, A-1, B and B/A-1 were predictive of subsequent risk. Those who would be eligible for lipid lowering Rx by National Cholesterol Education Program (NCEP) criteria, benefited from therapy. Rates of AMCE per 1000 person years were 1% (Lov) and 1.87% (Plc), relative risk (RR) = 0.53. Similarly, those who would not be eligible by NCEP criteria benefited with AMCE rates of 0.62% (Lov) and 0.93% (Plc), RR = 0.67. "As expected, NCEP Rx criteria predicted those who were at greater risk for AMCE's".

Abstract 1075-3 Airforce/Texas Coronary Atherosclerosis Prevention Study: Lipid Modification and Risk Associated with Non-Lipid Risk Factors

In this study, outlined in the preceding abstract, the following were confirmed to significantly affect ACME outcome: smoking, hypertension, age, family history of coronary heart disease (CHD), gender, baseline LDL and baseline HDL. Risk reduction for CHD with Lovastatin Rx was independent of non-lipid risk factors such as smoking, hypertension, gender, age and family history.

Abstract 1075-78 The Effects of Crystalline and Extended-Release Niacin, Niaspan on HDL Lipoprotein-Mediated Cellular Cholesterol Efflux as Compared to Placebo

Out of an on-going trial, 10 patients from each of 3 groups were selected; placebo (Plc), 1500 mg/day of crystalline niacin (niacin) and 1500 mg/day of extended release niacin (Niaspan). Cholesterol efflux potential for sera was measured, using a standardized cell culture system. Both niacin and Niaspan produced significant increases in HDL and cholesterol efflux. Percent change in HDL and efflux demonstrated a linear regression which correlated significantly for both niacin (r=0.63) and Niaspan (r=0.67). LDL did not correlate with efflux. The investigators state that the study suggests that the nicotinic acid effect on HDL leads to enhanced efflux of cellular cholesterol.

Abstract 1075-75 Simvastatin and Atorvastatin Have Different Effects on HDL Cholesterol and Apolipoprotein A-1

Atorvastatin (Atorv) in doses of 20 and 40 mg was compared with Simvastatin (Simv) in doses of 40 and 80 mg over a 12 week period in 842 patients with high cholesterol (41% women), randomized to one of the four treatment groups. At the low dose, Simv and Atorv produced only small differences in LDL lowering, -42.8% and -44.9%, respectively, (p<0.05), and similar TG lowering, -23% and -23.4%, respectively (p:NS). Similar results were seen with the high doses of Simv and Atorv for LDL; -48.9% and 51.1%, respectively (p<0.05), and for TG -25.3% and -29.6%, respectively (p<0.05). The differences, even when significant, were small in comparison to the substantial changes in LDL and TG brought about by each drug. In contrast, both doses of Simv produced an approximate doubling of the increase in HDL produced by Atorv; at the low dose, Simv produced a 6.7% increase in HDL vs 4.2% with Atorv (p<0.01). At the higher dose, Simv produced a 6.5% increase vs 3.1% with Atorv (p<0.01). A similar trend but somewhat different statistical result was seen with apo A-1. At low dose, Simv produced a 6.3% increase in apo A-1 and Atorv a 5.4% increase (p:NS). At the high dose, Simv produced a 5.7% increase in apo A-1 and Atorv a 0.3% decrease (p<0.001). The authors conclude by stating that the mechanisms underlying these differences are unknown and warrant investigation.