Effects of atorvastatin on Lp(a) and lipoprotein profiles in hemodialysis patients.

BACKGROUND: Dialysis patients have many underlying traditional and nontraditional risk factors that may predispose them to a high prevalence of cardiovascular disease. The effects of statins (eg, atorvastatin) on altering nontraditional lipoprotein measures in dialysis patients have not been extensively investigated. OBJECTIVE: To evaluate the efficacy of atorvastatin compared with a control group in inducing changes in lipoprotein(a) [Lp(a)], apolipoprotein (Apo) A-1, Apo-B, and fibrinogen levels, as well as the conventional lipoprotein profile, in hemodialysis patients over 36 weeks; secondary objectives were to assess changes in C-reactive protein, albumin, and safety measures. METHODS: Forty-five hemodialysis patients with low-density lipoprotein cholesterol (LDL-C) levels greater than 100 mg/dL were randomized to parallel groups: atorvastatin (n = 19) or no treatment (n = 26). The atorvastatin dose was titrated from 10 mg to achieve an LDL-C goal of 100 mg/dL or less and therapy was continued for 36 weeks. Biochemical and lipoprotein laboratory tests for efficacy outcomes were obtained at baseline, 12 weeks, and 36 weeks. RESULTS: The atorvastatin group exhibited clinically significant reductions (mean +/- SD) compared with controls in total cholesterol (-21.7 +/- 41.7 vs -3.2 +/- 40.0 mg/dL, respectively; p = 0.017) and LDL-C (-13.1 +/- 32.0 vs -1.1 +/- 38.4 mg/dL, respectively; p = 0.058) levels, as well as Lp(a) (-10.6 +/- 27 vs 3.5 +/- 17.8 mg/dL, respectively; p = 0.046). Statistical analyses included analysis of variance on ranked measures for multivariable modeling and paired t-test to determine changes in efficacy measures between baseline and 36 weeks within groups. CONCLUSIONS: Atorvastatin was safe and effective in reducing Lp(a), total cholesterol, and LDL-C levels. Given the prevalence of atherosclerosis in hemodialysis patients, therapy aimed at reducing traditional and nontraditional risk factors may be beneficial.

Effects of atorvastatin on low-density lipoprotein cholesterol phenotype and C-reactive protein levels in patients undergoing long-term dialysis.

STUDY OBJECTIVES: To determine the effects of atorvastatin on low-density lipoprotein cholesterol (LDL) particle size and C-reactive protein (CRP) concentrations in patients undergoing long-term hemodialysis. Another objective was to compare the effects of atorvastatin on lipoprotein profiles as determined by direct versus indirect assessment of lipoprotein composition. DESIGN: Randomized, parallel-group substudy. SETTING: Two university-affiliated outpatient hemodialysis centers. PATIENTS: Nineteen patients with LDL levels above 100 mg/dl and with at least two cardiovascular risk factors. INTERVENTION: Patients were randomized in a 1:1 ratio to atorvastatin 10 mg/day or no treatment (control) for 20 weeks. MEASUREMENTS AND MAIN RESULTS: We compared the differences between LDL particle size and CRP levels at baseline and 20 weeks in the atorvastatin versus control groups. Baseline demographic characteristics were similar between the two groups. Atorvastatin therapy was associated with no change in mean LDL particle size (p=0.23) and with a 90% decrease in mean CRP level (p=0.52). When evaluated by standard chemical analysis, atorvastatin therapy reduced total cholesterol levels by 29% (p=0.025) and resulted in nonsignificant reductions in LDL, high-density lipoprotein cholesterol, and triglyceride levels. Treatment with atorvastatin was not associated with significant changes in lipoprotein profile as determined by nuclear magnetic resonance (NMR) spectroscopy. CONCLUSION: Treatment with atorvastatin did not affect LDL particle size but was associated with a sizable, yet nonsignificant, reduction in CRP concentrations. The drug had variable effects on lipoprotein concentrations as determined by chemical and NMR analytical methods. A larger study is necessary to provide definitive information on the effects of atorvastatin on LDL phenotype and CRP in patients with kidney disease.

Secondary prevention of coronary heart disease in the elderly.

OBJECTIVE: To review relevant literature supporting the use of aspirin, beta-blockers, lipid-lowering agents, and angiotensin-converting enzyme (ACE) inhibitors for the secondary prevention of coronary heart disease (CHD) in an elderly patient population aged >/=65 years. DATA SOURCES: A MEDLINE search (1990-May 2003) was conducted using the key terms coronary heart disease, secondary prevention and elderly. STUDY SELECTION AND DATA EXTRACTION: Primary and tertiary literature relating to the use of aspirin, beta-blockers, lipid-lowering agents, and ACE inhibitors in the elderly were reviewed. DATA SYNTHESIS: CHD is the leading cause of morbidity and mortality in persons >/=65 years of age, and the use of pharmacologic agents has created a considerable opportunity for reducing recurrent events in those with established disease. This, combined with the aging of the US population, is creating an increase in the number of older adults eligible for secondary prevention. In 2002, the American Heart Association issued a scientific statement on the benefits of specific secondary prevention risk factor interventions in older adults. This article reviews pertinent findings from this statement, along with additional data supporting the use of pharmacologic agents for the secondary prevention of CHD in the elderly. CONCLUSIONS: Data suggest that use of aspirin, beta-blockers, lipid-lowering agents, and ACE inhibitors are effective in secondary prevention of CHD in individuals aged >/=65 years. This benefit is similar to, and often greater than, that observed in younger patients. We believe that these agents should be prescribed for all elderly patients without contraindications. Ongoing studies and future clinical trials will more clearly elucidate the benefits of secondary prevention of CHD, particularly in persons >/=75 years of age, to determine the magnitude of benefits that can be achieved in this population.

Primary prevention of coronary heart disease in the elderly.

OBJECTIVE: To review relevant literature supporting the use of antihypertensive agents, lipid-lowering agents (i.e., statins), and aspirin therapy for the primary prevention of coronary heart disease (CHD) in an elderly patient population (age >or=65 y). DATA SOURCES: A MEDLINE search (1988-January 2003) was conducted. STUDY SELECTION AND DATA EXTRACTION: Primary and tertiary literature involving the uses of antihypertensives, statins, and aspirin therapy in the elderly were reviewed. DATA SYNTHESIS: Mortality due to CHD in the US population has decreased 40-50% over the last 30 years; however, CHD remains the leading cause of morbidity and mortality in elderly persons. As the population continues to age, the number of older adults eligible for primary prevention will rise. The American Heart Association clinical practice guidelines for the primary prevention of CHD were updated in 2002; however, they are based on findings from clinical trials that enrolled predominantly middle-aged white men. The recommendations for elderly individuals are predominantly extrapolated from subgroup analyses of randomized clinical trials or cohort studies. This literature suggests that elderly persons are candidates for primary prevention measures and experience reductions in coronary events when treated with appropriate therapies. CONCLUSIONS: Data suggest that use of antihypertensives, statins, and aspirin therapy in the elderly appears effective to an extent similar to, and often greater than, that observed in younger patients. We believe these agents should be prescribed to all appropriate high-risk elderly patients. Ongoing and future studies will more clearly elucidate the benefits of primary prevention therapy, particularly in persons >or=75 years of age.

Genetic polymorphisms in emerging cardiovascular risk factors and response to statin therapy.

Current strategies for both the primary and secondary prevention of coronary heart disease (CHD) focus on the traditional risk factors, such as hypertension, smoking cessation, and cholesterol, as the primary determinants of the cardiac risk profile, with particular emphasis on the reduction of low-density lipoprotein cholesterol (LDL-C) to targeted goal levels as endorsed by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATPIII). Large primary and secondary prevention trials with the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have demonstrated varying reductions in cardiovascular events associated with similar changes in LDL-C levels, suggesting statins may possess additional beneficial effects on other risk factors. Retrospective analyses of many statin trials have evaluated the association between several polymorphic candidate genes (apolipoprotein E, stromelysin-1, beta-fibrinogen, cholesteryl ester transfer protein, lipoprotein lipase, hepatic lipase, and platelet glycoprotein III) which have been identified as predictors of disease severity and both metabolic and clinical response to statin therapy. These results suggest that statin therapy improves plasma lipid profiles in all patients, but preferentially benefits individuals who carry a high risk, variant genotype for these risk factors as compared to individuals with the wild-type genotype. These observations suggest that determining individual patient genotype may be useful in optimizing the benefits of statin therapy. These hypothesis-generating data need to be prospectively evaluated in genotyped patients.