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Biomedical subjects

C M Ballantyne

Publications and source records attributed to C M Ballantyne.

At least 19 recordsLinked to original sources
PubMed2001

Influence of low high-density lipoprotein cholesterol and elevated triglyceride on coronary heart disease events and response to simvastatin therapy in 4S.

BACKGROUND: Patients with low HDL cholesterol (HDL-C) and elevated triglyceride had an increased risk for coronary heart disease (CHD) events and received the greatest benefit with fibrate therapy in substudy analyses of the Helsinki Heart Study and the Bezafibrate Infarction Prevention Study. METHODS AND RESULTS: In this post hoc analysis of the Scandinavian Simvastatin Survival Study, which enrolled patients with elevated LDL cholesterol (LDL-C) and CHD, subgroups defined by HDL-C and triglyceride quartiles were compared to examine the influence of HDL-C and triglyceride on CHD events and response to therapy. Patients in the lowest HDL-C (<1.00 mmol/L [39 mg/dL]) and highest triglyceride (>1.80 mmol/L [159 mg/dL]) quartiles (lipid triad; n=458) had increased proportions of other features of the metabolic syndrome (increased body mass index, hypertension, diabetes), men, prior myocardial infarction, prior revascularization, and beta-blocker use than patients in the highest HDL-C (>1.34 mmol/L [52 mg/dL]) and lowest triglyceride (<1.11 mmol/L [98 mg/dL]) quartiles (isolated LDL-C elevation; n=545). The major coronary event rate was highest in lipid triad patients on placebo (35.9%), and this subgroup had the greatest event reduction (relative risk 0.48, 95% CI 0.33 to 0.69); a significant treatment-by-subgroup interaction (P=0.03) indicated a greater treatment effect in the lipid triad subgroup than the isolated LDL-C elevation subgroup. CONCLUSIONS: Patients with elevated LDL-C, low HDL-C, and elevated triglycerides were more likely than patients with isolated LDL-C elevation to have other characteristics of the metabolic syndrome, had increased risk for CHD events on placebo, and received greater benefit with simvastatin therapy.

Adult↗
PubMed2001

Effect of sirolimus on the metabolism of apoB100- containing lipoproteins in renal transplant patients.

BACKGROUND: Sirolimus (Rapamune, rapamycin, RAPA) is a potent immunosuppressive drug that has reduced the rate of acute rejection episodes by more than 40% in phase III trials when added to an immunosuppression regimen of cyclosporine (CsA) and prednisone. However, RAPA treatment tends to increase lipid levels, particularly among patients with pre-existing hyperlipidemia. METHODS: To identify the metabolic pathway(s) leading to RAPA-mediated hyperlipidemia, five patients with renal transplants maintained on CsA+/-prednisone+/- azathioprine (AZA) were studied before and after 6 weeks of treatment with RAPA (off RAPA and on RAPA, respectively). Each study patient was infused with a single bolus of [2H4]-lysine to derive metabolic parameters for apoB100-containing lipoproteins by using kinetic analysis based upon quantitation of isotopic enrichment by gas chromatography-mass spectrometry. RESULTS: Serial lipid measurements revealed that four patients displayed increased plasma triglyceride levels after RAPA treatment, which coincided with significantly higher plasma VLDL-apoB100 concentrations (21.7+/-12.1 mg/dl off RAPA vs. 38.7+/-14.8 mg/dl on RAPA, mean+/-SD, P<0.05). Kinetic analysis showed that the RAPA-induced increase in VLDL-apoB100 concentrations was due to a significant reduction in the fractional catabolic rate (FCR) of very low-density lipoprotein (VLDL) apoB100 (0.83+/-0.65 off RAPA vs. 0.24+/-0.10 on RAPA, mean+/-SD, P<0.05), rather than an enhanced VLDL-apoB100 synthesis. In one patient, RAPA treatment induced hypercholesterolemia but not hypertriglyceridemia. This hypercholesterolemia was due to elevated low-density lipoprotein (LDL) cholesterol levels, which coincided with a decreased FCR of LDL-apoB100. Heparin-induced lipoprotein lipase activity was significantly lower in the immunosuppressed hyperlipidemic patients than in normolipidemic controls. However, RAPA treatment did not significantly alter basal lipoprotein lipase activity in renal transplant patients in this study. CONCLUSIONS: This study indicates that for renal transplant patients in whom RAPA treatment induces hyperlipidemia, this effect is the result of reduced catabolism of apoB100-containing lipoproteins.

Apolipoprotein B-100↗
PubMed2001

Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Despite consensus on the need for blood cholesterol reductions to prevent coronary heart disease (CHD), available evidence on optimal cholesterol levels or the added predictive value of additional lipids is sparse. METHODS AND RESULTS: After 10 years follow-up of 12 339 middle-aged participants free of CHD in the Atherosclerosis Risk in Communities Study (ARIC), 725 CHD events occurred. The lowest incidence was observed in those at the lowest LDL cholesterol (LDL-C) quintile, with medians of 88 mg/dL in women and 95 mg/dL in men, and risk accelerated at higher levels, with relative risks (RRs) for the highest quintile of 2.7 in women and 2.5 in men. LDL-C, HDL-C, lipoprotein(a) [Lp(a)], and in women but not men, triglycerides (TG) were all independent CHD predictors, providing an RR, together with blood pressure, smoking, and diabetes, of 13.5 in women and 4.9 in men. Lp(a) was less significant in blacks than whites. Prediction was not enhanced by HDL-C density subfractions or apolipoproteins (apo) A-I or B. Despite strong univariate associations, apoB did not contribute to risk prediction in subgroups with elevated TG, with lower LDL-C, or with high apoB relative to LDL-C. CONCLUSIONS: Optimal LDL-C values are <100 mg/dL in both women and men. LDL-C, HDL-C, TG, and Lp(a), without additional apolipoproteins or lipid subfractions, provide substantial CHD prediction, with much higher RR in women than men.

Apolipoprotein A-I↗
PubMed2001

Achieving and maintaining National Cholesterol Education Program low-density lipoprotein cholesterol goals with five statins.

PURPOSE: Most patients fail to achieve and maintain low-density lipoprotein (LDL) cholesterol goals established by the National Cholesterol Education Program (NCEP). The Atorvastatin Comparative Cholesterol Efficacy and Safety Study (ACCESS) was a randomized study comparing the efficacy and safety of five statins and their ability reduce LDL cholesterol to the NCEP target level. SUBJECTS AND METHODS: Of 7542 patients screened, 3916 hypercholesterolemic patients were randomly assigned to treatment with a statin, beginning with the lowest recommended dose (atorvastatin, pravastatin, and simvastatin, 10 mg; fluvastatin and lovastatin, 20 mg). If the NCEP target was not achieved, the dose was titrated up to the recommended maximum (atorvastatin, fluvastatin, and lovastatin, 80 mg; pravastatin and simvastatin, 40 mg). The total duration of treatment was 54 weeks. RESULTS: Atorvastatin achieved the greatest mean reduction in LDL cholesterol: 36% +/- 11% at 6 weeks (initial dose) and 42% +/- 13% at 54 weeks. More patients receiving atorvastatin at its initial dose (53%, 997 of 1888) achieved their NCEP target levels than patients receiving simvastatin (38%, 174 of 462), lovastatin (28%, 134 of 472), pravastatin (15%, 71 of 461), or fluvastatin (15%, 69 of 474) at the initial dose. Atorvastatin-treated patients were more likely to maintain their target levels from week 6 to week 54. The percent reduction in LDL cholesterol achieved at the initial dose correlated strongly with the proportion of patients who maintained their goals at 54 weeks (r = -0.84). CONCLUSION: For patients treated with statins, providing a greater margin between the NCEP target level and the achieved LDL cholesterol level enhances the likelihood of maintaining NCEP goal levels.

Aged↗
PubMed2001

Correlation of non-high-density lipoprotein cholesterol with apolipoprotein B: effect of 5 hydroxymethylglutaryl coenzyme A reductase inhibitors on non-high-density lipoprotein cholesterol levels.

Apolipoprotein B has been shown to be a better predictor of coronary heart disease than low-density lipoprotein (LDL) cholesterol, and non-high-density lipoprotein (non-HDL) cholesterol may also be a better parameter for coronary heart disease risk assessment and as a target for therapy. Data from the Atorvastatin Comparative Cholesterol Efficacy and Safety Study (ACCESS) were used to assess the correlation between lipid and apolipoprotein B levels before and after lipid-lowering therapy and to examine the effects of 5 hydroxymethylglutaryl coenzyme A reductase inhibitors on lipids and apolipoprotein B. The 54-week study randomized 3,916 hypercholesterolemic patients to atorvastatin, fluvastatin, lovastatin, pravastatin, or simvastatin, initiated at recommended starting doses with titrations as needed at weeks 6, 12, and 18 to achieve National Cholesterol Education Program LDL targets. Compared with LDL cholesterol, non-HDL cholesterol correlated better with apolipoprotein B levels at baseline (r = 0.914, p <0.0001) and at week 54 (r = 0.938, p <0.0001), and the correlation was strong across all baseline triglyceride strata. At starting doses, atorvastatin (10 mg) lowered non-HDL cholesterol by 33.3% compared with 26.6% with simvastatin (10 mg), 24.1% with lovastatin (20 mg), 17.2% with fluvastatin (20 mg), and 17.0% with pravastatin (10 mg). Atorvastatin also provided greater reductions in non-HDL cholesterol after dose titration, and a greater percentage of patients taking atorvastatin achieved non-HDL cholesterol targets. Baseline triglyceride did not affect non-HDL cholesterol reductions with any of the 5 hydroxymethylglutaryl coenzyme A reductase inhibitors. Fewer patients achieved non-HDL cholesterol targets than LDL cholesterol targets, particularly among high-risk patients, implying that if non-HDL cholesterol was used as a target for treatment, more patients would need to be treated more aggressively than National Cholesterol Education Program guidelines require.

Anticholesteremic Agents↗
PubMed2001

The differential roles of LFA-1 and Mac-1 in host defense against systemic infection with Streptococcus pneumoniae.

Mice deficient in CD18, which lack all four CD11 integrins, have leukocytosis and increased susceptibility to bacterial infection. To determine the effect of deficiencies in LFA-1 (CD11a/CD18) or Mac-1 (CD11b/CD18) on host defense against systemic bacterial infection, knockout mice were inoculated i.p. with Streptococcus pneumoniae. Increased mortality occurred in both LFA-1(-/-) (15 of 17 vs 13 of 35 in wild type (WT), p < 0.01) and Mac-1(-/-) (17 of 34 vs 6 of 25, p < 0.01) mice. All deaths in LFA-1(-/-) mice occurred after 72 h, whereas most deaths in Mac-1(-/-) mice occurred within 24-48 h. At 24 h, 21 of 27 Mac-1(-/-) mice were bacteremic, vs 15 of 25 WT (p = 0.05); no difference was observed between LFA-1(-/-) and WT. Increased bacteria were recovered from Mac-1(-/-) spleens at 2 h (p = 0.03) and 6 h (p = 0.002) and from livers (p = 0.001) by 6 h. No difference was observed at 2 h in LFA-1(-/-) mice, but by 6 h increased bacteria were recovered from spleens (p = 0.008) and livers (p = 0.04). Baseline and peak leukocyte counts were similar between Mac-1(-/-) and WT, but elevated in LFA-1(-/-). At 8 h, peritoneal neutrophils were increased in Mac-1(-/-), but not significantly different in LFA-1(-/-). Histopathologically, at 24 h Mac-1(-/-) animals had bacteremia and lymphoid depletion, consistent with sepsis. LFA-1(-/-) mice had increased incidence of otitis media and meningitis/encephalitis vs WT at 72 and 96 h. Both Mac-1 and LFA-1 play important but distinct roles in host defense to S. pneumoniae.

Animals↗
PubMed2001

Novel polymorphisms in promoter region of atp binding cassette transporter gene and plasma lipids, severity, progression, and regression of coronary atherosclerosis and response to therapy.

Identification of mutations in the ATP binding cassette transporter (ABCA1) gene in patients with Tangier disease, who exhibit reduced HDL cholesterol (HDL-C) and apolipoprotein A1 (apoA1) levels and premature coronary atherosclerosis, has led to the hypothesis that common polymorphisms in the ABCA1 gene could determine HDL-C and apoA1 levels and the risk of coronary atherosclerosis in the general population. We sequenced a 660-bp 5' fragment of the ABCA1 gene in 24 subjects and identified 3 novel polymorphisms: -477C/T, -419A/C, and -320G/C. We developed assays, genotyped 372 participants in the prospective Lipoprotein Coronary Atherosclerosis Study (LCAS), and determined the association of the variants with fasting plasma lipids and indices of quantitative coronary angiograms obtained at baseline and 2.5 years after randomization to fluvastatin or placebo. Distribution of -477C/T and -320G/C genotypes were 127 CC, 171 CT, and 74 TT and 130 GG, 168 GC, and 75 CC, respectively, and were in complete linkage disequilibrium (P<0.0001). Data for -477C/T are presented. The -419A/C variant was uncommon (present in 1 of 63 subjects). Heterozygous subjects had a modest reduction in HDL-C (P=0.09) and apoA1 (P=0.05) levels and a lesser response of apoA1 to treatment with fluvastatin (P=0.04). The mean number of coronary lesions causing 30% to 75% diameter stenosis was greater in subjects with the TT genotype (3.1+/-2.1) or CT genotype (2.9+/-1.9) than in subjects with the CC genotype (2.2+/-1.8) (P=0.002). Similarly, compared with subjects with the CC genotype, greater numbers of subjects with the TT or CT genotype had >/=1 coronary lesion (P=0.001). No association between the genotypes and progression of coronary atherosclerosis or clinical events was detected. We conclude that ABCA1 genotypes are potential risk factors for coronary atherosclerosis in the general population.

ATP Binding Cassette Transporter 1↗
PubMed2001

Case 4: type 2 diabetes, hypertension, and dyslipidemia.

Patients at risk for coronary heart disease often have multiple underlying risk factors, including hypertension, type 2 diabetes mellitus, and dyslipidemia. The focus of this month's CME case study is recognition of these often silent and coexisting diseases, and the selection of appropriate therapy that will not adversely affect management of comorbid conditions.

Coronary Disease↗
PubMed2001

A prospective study of paraoxonase gene Q/R192 polymorphism and severity, progression and regression of coronary atherosclerosis, plasma lipid levels, clinical events and response to fluvastatin.

Human serum paraoxonase (PON1) is a high-density lipoprotein (HDL)-associated enzyme that is responsible for the protective effect of HDL against oxidation of low-density lipoprotein (LDL). PON1 has a Glu to Arg polymorphism at codon 192 (CGA-->CAA) which is designated R/Q192. The R/Q192 polymorphism has been associated with coronary artery disease (CAD) in several, but not all, case-control studies. We prospectively studied the association of the Q/R192 genotypes with the severity, progression and regression of CAD, plasma lipid levels, clinical events and response to treatment with fluvastatin in a well-characterized cohort. Genotypes were determined by polymerase chain reaction (PCR) and restriction mapping with AlwI enzyme in 356 subjects in the Lipoprotein and Coronary Atherosclerosis Study (LCAS). Fasting plasma lipids were measured and quantitative coronary angiograms were obtained at baseline and 2.5 years following randomization to fluvastatin or placebo. A total of 177 (50%), 142 (40%) and 37 (10%) subjects had Q/Q, Q/R and R/R genotypes, respectively. Baseline and final plasma levels of HDL, LDL, triglyceride and other lipoproteins, lesion-specific minimum lumen diameters (MLD), mean MLD, number of coronary lesions and total occlusions at baseline and follow-up and clinical event rates were not significantly different among the genotypes. There was no genotype-treatment interaction with respect to plasma lipid levels and angiographic indices of CAD. The Q/R192 variants of PON1 are not associated with severity, progression or regression of coronary atherosclerosis, plasma lipid levels, clinical events, or response to treatment with fluvastatin. Thus, the Q/R192 polymorphism is not a major risk factor in susceptibility to CAD in the LCAS population.

Aged↗
PubMed2001

Treating mixed dyslipidemias: why and how.

Patients with only mildly elevated low-density lipoprotein cholesterol values but low high-density lipoprotein cholesterol (HDL-C) and/or high triglyceride levels are at high risk for cardiovascular disease. 3-Hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (also known as statins) have been shown to slow coronary heart disease (CHD) progression, reduce CHD events in patients with low HDL-C levels, and raise HDL-C concentrations in patients with mixed dyslipidemias. Some, but not all trials of fibrates have shown benefit in patients with low HDL-C levels. Combination therapy with a statin plus either a fibrate or niacin is effective in improving the entire lipid profile, but may increase cost and side effects.

Cholesterol, HDL↗
PubMed2001

Newer risk markers and surrogate endpoints in atherosclerosis management.

Risk markers that allow improved and individualized assessment of atherosclerotic disease risk and response to treatment are needed. Current candidate markers include cell adhesion molecules, such as intercellular adhesion molecule-1 and E-selectin, and inflammatory markers, such as C-reactive protein; advances in genomics and proteomics will suggest additional candidate markers. Noninvasive imaging procedures such as electron-beam computed tomography and magnetic resonance imaging also show considerable promise for monitoring disease status and response to treatment, and ultimately could provide surrogate endpoints for clinical trials of therapeutic interventions.

Biomarkers↗
PubMed2001

Efficacy and tolerability of fluvastatin extended-release delivery system: a pooled analysis.

BACKGROUND: At high doses, the pharmacokinetics of fluvastatin immediate-release (IR) are nonlinear, possibly due to saturation of hepatic uptake. Fluvastatin delivery to the liver in a slower but sustained fashion would be expected to avoid hepatic saturation without elevating systemic drug levels. OBJECTIVE: This pooled analysis compared the efficacy and tolerability of extended-release (XL) 80-mg and IR 40-mg formulations of fluvastatin in lowering low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and raising high-density lipoprotein cholesterol (HDL-C) levels in patients with hypercholesterolemia. METHODS: Data were pooled from 3 double-blind, randomized, active-controlled, multicenter, parallel-group studies that compared changes in lipid and apolipoprotein levels with fluvastatin XL 80 mg at bedtime (HS) with changes in fluvastatin IR 40 mg HS or BID in patients aged > or =18 years with primary hypercholesterolemia (consistently elevated LDL-C level [> or =160 mg/dL] and plasma TG levels < or =400 mg/dL). The primary efficacy variable was percent change in LDL-C from baseline. RESULTS: The pooled analysis provided an intent-to-treat efficacy study population of 1674 patients. At 4 weeks, fluvastatin XL 80 mg HS reduced LDL-C levels by a mean of 36.3% (median 38%), significantly greater than a mean reduction of 25.9% (median 27%) seen with fluvastatin IR 40 mg HS, and an incremental additional mean reduction in LDL-C of 10.4% (P < 0.001). At 4 and 24 weeks, fluvastatin XL 80 mg HS provided an LDL-C reduction equivalent to fluvastatin IR 40 mg BID (P < 0.001 for noninferiority). Significant, dose-related changes in HDL-C, LDL-C:HDL-C ratio, total cholesterol, TG, and apolipoprotein A-I and apolipoprotein B levels also occurred. Mean HDL-C level increased by 8.7% and median TG level decreased by 19% with fluvastatin XL 80 mg HS (P < 0.001 and P < 0.05 vs fluvastatin IR 40 mg HS, respectively). Maximum mean increases in HDL-C level (21%) and median decreases in TG level (31%) with fluvastatin XL 80 mg HS occurred in patients with type IIb dyslipidemia and the highest baseline TG. Adverse events were mild, with similar frequency in all treatment groups. CONCLUSIONS: Once-daily administration of fluvastatin XL 80 mg provides enhanced efficacy with an additional 10.4% reduction in LDL-C levels compared with fluvastatin IR 40 mg HS, and superior increases in HDL-C levels, particularly in patients with elevated TG levels (P < 0.05 vs fluvastatin IR 40 mg HS). Fluvastatin XL 80 mg HS has a good tolerability profile and is effective as starting and maintenance lipid-lowering treatment in patients with type II hypercholesterolemia.

Adult↗
PubMed2001

The evolving role of high-density lipoprotein in reducing cardiovascular risk.

In many patients with coronary artery disease, a low level of high-density lipoprotein cholesterol (HDL-C), rather than substantially elevated low-density lipoprotein cholesterol (LDL-C), is often the predominant lipid abnormality. Although the National Cholesterol Education Program treatment guidelines include HDL-C concentration as a major risk factor for primary prevention, the guidelines' emphasis on LDL-C as the primary target of therapy may cause uncertainty as to whether risk reduction strategies should focus on lowering LDL-C or raising HDL-C in high-risk patients with low HDL-C. Recent clinical trial evidence and epidemiologic data suggest that HDL-C should play a more important role in risk assessment, and that the definition of low HDL-C may need adjustment from the current National Cholesterol Education Program definition of <35 mg/dL to perhaps <40 mg/dL in men and <45 mg/dL in women. Patients with low HDL-C should receive aggressive risk factor modification, and more emphasis on increasing HDL-C may be warranted in addition to lowering LDL-C. (c) 2001 by CHF, Inc.

Journal Article↗
PubMed2001

Leukocyte trafficking and myocardial reperfusion injury in ICAM-1/P-selectin-knockout mice.

P-selectin and intercellular adhesion molecule-1 (ICAM-1) mediate early interaction and adhesion of neutrophils to coronary endothelial cells and myocytes after myocardial ischemia and reperfusion. In the present study, we examined the physiological consequences of genetic deletions of ICAM-1 and P-selectin in mice. In wild-type mice, after 1 h of ischemia followed by reperfusion, neutrophil influx into the area of ischemia was increased by 3 h with a peak at 24 h and a decline by 72 h. ICAM-1/P-selectin-deficient mice showed a significant reduction in neutrophils by immunohistochemistry or by myeloperoxidase activity at 24 h but no significant difference at 3 h. Infarct size (area of necrosis/area at risk) assessed 24 h after reperfusion was not different between wild-type and deficient mice after 30 min and 1 h of occlusion. Mice with a deficiency in both ICAM-1 and P-selectin have impaired neutrophil trafficking without a difference in infarct size due to myocardial ischemia-reperfusion.

Animals↗
PubMed2001

Surrogate endpoints and newer risk markers in atherosclerosis management.

Trials with clinical events as the primary endpoint inherently have poor sensitivity to detect therapeutic effects on plaque stabilization and thrombosis because most plaques that rupture do not cause symptoms. Blood tests or imaging modalities that correlate to the burden or activity of atherosclerosis may provide surrogate endpoints to assess therapeutic efficacy in both clinical trials and clinical practice. For surrogate endpoints to be valid in clinical trials, they must be biologically plausible (i.e., related to the disease process) and altered by therapies that decrease the endpoint for which they are used as a substitute. Examples of surrogate endpoints include progression of coronary disease assessed by angiography, intravascular ultrasound, and other imaging techniques. Risk assessment may be refined and therapy better monitored with blood tests that measure novel markers of atherosclerotic disease. Markers that have been shown to be associated with atherosclerosis include C-reactive protein, intercellular adhesion molecule 1, interleukin-6, and fibrinogen.

Arteriosclerosis↗
PubMed2000

Apolipoprotein E genotypes and response of plasma lipids and progression-regression of coronary atherosclerosis to lipid-lowering drug therapy.

OBJECTIVES: We sought to examine the association of apolipoprotein (apo) E genotypes with baseline plasma lipid levels and severity of coronary artery disease (CAD), as well as the response to treatment with fluvastatin in the Lipoprotein and Coronary Atherosclerosis Study (LCAS). BACKGROUND: Apo E genotypes have been associated with plasma lipid levels and CAD. However, the influence of apo E genotypes on the response of plasma lipids and CAD progression or regression to statin treatment in patients with mildly to moderately elevated cholesterol remains unknown. METHODS: Apo E genotypes were determined by polymerase chain reaction and restriction mapping. Plasma lipids were measured at baseline and 12 weeks after therapy with fluvastatin or placebo in 320 subjects. In 287 subjects, quantitative coronary angiography was performed at baseline and after 2.5 years of treatment. RESULTS: Subjects with the 3/3 genotype had greater reductions in total cholesterol (20.4% vs. 15.4%, p = 0.01) and low density lipoprotein (LDL) cholesterol (28.8% vs. 22.7%, p = 0.03) than did the subjects with the 3/4 or 4/4 genotype. In contrast, subjects with the 2/3 genotype (n = 10) had a greater increase in high density lipoprotein cholesterol (19.1%) than did the subjects with the 3/3 genotype (4.3%, p = 0.002) and those with the 3/4 or 4/4 genotype (7.0%, p = 0.02). Subjects with the 3/4 or 4/4 genotype had an increased frequency of previous angioplasty, but other measures of baseline CAD severity and baseline lipids did not differ significantly among the genotypes, nor did CAD progression or clinical events. CONCLUSIONS: Although subjects with the epsilon4 allele had less reduction in LDL cholesterol with fluvastatin, they had similar benefit in terms of CAD progression.

Anticholesteremic Agents↗