Effect Of Cholesterol Lowering Research Articles

Lipids and Cognition

Cholesterol, omega-3 fatty acids, and triglycerides have been postulated to play roles in affecting cognition in Alzheimer's disease (AD), the elderly, and obesity. Animal, human epidemiological, and in vitro studies each suggest an important role for cholesterol in the regulation of amyloid-beta (Abeta) protein and the pathogenesis of AD. In contrast, well controlled studies have failed to show an effect of cholesterol lowering with statins on cognition, indicating that the cholesterol effect is spurious or indirect, possibly mediated through other lipids. Administration of diedocosahexanoic acid (DHA), a dietary omega-3 fatty acid derived primarily from fish and plants, improves cognition and reduces lipid peroxidation in animals, including in mouse models of AD. DHA also blocks Abeta-mediated tau phosphorylation. In humans, fish consumption or administration of DHA has been associated with cognitive improvement in many, but not all, studies. Both human and animal studies show that obesity is associated with cognitive impairments and that lowering triglycerides improves cognition. Administration of triglycerides to mice decreases learning and memory and impairs long-term potential. The effect of triglycerides may be mediated in part by inducing resistance to positive cognitive features of gastrointestinal hormones such as leptin. Overall, these studies strongly suggest that some lipids affect cognition in AD, the elderly, and obesity through a variety of mechanisms yet to be fully defined.

Effect of Lipid Lowering With Rosuvastatin on Progression of Aortic Stenosis

Aortic stenosis (AS) is an active process with similarities to atherosclerosis. The objective of this study was to assess the effect of cholesterol lowering with rosuvastatin on the progression of AS. This was a randomized, double-blind, placebo-controlled trial in asymptomatic patients with mild to moderate AS and no clinical indications for cholesterol lowering. The patients were randomized to receive either placebo or rosuvastatin 40 mg daily. A total of 269 patients were randomized: 134 patients to rosuvastatin 40 mg daily and 135 patients to placebo. Annual echocardiograms were performed to assess AS progression, which was the primary outcome; the median follow-up was 3.5 years. The peak AS gradient increased in patients receiving rosuvastatin from a baseline of 40.8+/-11.1 to 57.8+/-22.7 mm Hg at the end of follow-up and in patients with placebo from 41.6+/-10.9 mm Hg at baseline to 54.8+/-19.8 mm Hg at the end of follow-up. The annualized increase in the peak AS gradient was 6.3+/-6.9 mm Hg in the rosuvastatin group and 6.1+/-8.2 mm Hg in the placebo group (P=0.83). Treatment with rosuvastatin was not associated with a reduction in AS progression in any of the predefined subgroups. Cholesterol lowering with rosuvastatin 40 mg did not reduce the progression of AS in patients with mild to moderate AS; thus, statins should not be used for the sole purpose of reducing the progression of AS. Clinical Trial Registration Information- URL: http://www.controlled-trials.com/. ISRCTN 32424163.

Risk factors for stroke and lipid-lowering effect of pravastatin on the risk of stroke in Japanese patients with hypercholesterolemia: Analysis of data from the MEGA Study, a large randomized controlled trial

BackgroundThe aims of this study were to clarify the risk factors for stroke, and to investigate the effect of low-density lipoprotein cholesterol (LDL-C) lowering with pravastatin on the risk of stroke, in Japanese mild-to-moderately hypercholesterolemic patients enrolled in the MEGA Study. MethodsMultivariate Cox proportional hazard model was used to determine the baseline risk factors for stroke. The proportion of treatment effect (PTE) explained by on-treatment LDL-C levels was estimated. ResultsIn 7832 patients at risk, a total of 99 strokes were observed during the 5-year follow-up period. Significant relationships were observed between stroke and traditional risk factors such as male sex, advanced age, low high-density lipoprotein cholesterol (HDL-C), high lipoprotein(a) (Lp[a]), hypertension, diabetes, obesity, and smoking. In the pravastatin group, hazard ratio (HR) for stroke adjusted by on-treatment lipid level was lower than the unadjusted value versus control (HR [95%CI], 0.48 [0.26–0.87] and 0.59 [0.38–0.92], respectively)—giving a negative PTE of −38.6% and suggesting that the risk reduction could not be explained by LDL-C lowering alone. ConclusionsMale sex, aging, hypertension, diabetes, low HDL-C, high Lp(a), obesity, and smoking were determined as risk factors for stroke in Japanese patients with hypercholesterolemia, and the observed risk reduction could not be explained by pravastatin's LDL-C-lowering effect alone, suggesting pleiotropic effects.

The effects of dietary cholesterol-lowering on psychological symptoms: A randomised controlled study

The relationship of plasma cholesterol-reducing interventions to emotional states, such as depression and hostility, remains a topic of debate. The present study employed a randomised, controlled design, and was conducted at a clinical research center to test the effect of dietary cholesterol-lowering on psychological symptoms. Ten women and eight men were randomly assigned to one of two counterbalanced diet cycles (low-fat versus high-fat diet; isocaloric; 6 weeks each; separated by a washout period). Analyses for repeated measures revealed that the low-fat diet significantly reduced total, LDL and HDL cholesterol, when compared with baseline and the high-fat diet. As expected, weight remained unchanged. Ratings of depression, hostility and global severity of psychological symptoms as measured by the SCL-90-R also improved significantly on the low-fat, high-complex carbohydrate diet when compared with baseline. These results suggest that plasma cholesterol-lowering in the context of a low-fat, high-complex carbohydrate diet may have a beneficial effect on psychological symptoms.

The Complex Relationship Between Cholesterol and Brain Hemorrhage

In this issue of Circulation , Noda et al1 report an association between low levels of low-density lipoprotein cholesterol (LDL-C) and an increase in the risk of fatal intraparenchymal intracerebral hemorrhage in a Japanese population-based cohort. The relationship between lipid levels and stroke is complex. The Prospective Studies Collaboration conducted a meta-analysis evaluating the association between blood cholesterol and vascular mortality based on data from 61 prospective cohort studies including nearly 900 000 persons free of vascular disease at baseline (11.6 million person-years at risk).2 Lower levels of usual total cholesterol were strongly associated with lower risk of fatal ischemic heart disease; every 1 mmol/L lower cholesterol was associated with a 56% reduction (hazard ratio [HR], 0.44; 95% CI, 0.42 to 0.48) in those 40 to 49 years of age, a 34% reduction (HR, 0.66; 95% CI, 0.65 to 0.68) in those 50 to 69 years of age, and a 17% reduction (HR, 0.83; 95% CI, 0.81 to 0.85) in those 70 to 89 years of age. In contrast to death resulting from ischemic heart disease, there was only a weak relationship between usual total cholesterol and death caused by stroke in those 40 to 59 years of age (HR, 0.90; 95% CI, 0.84 to 0.97 for every 1 mmol/L lower cholesterol) and no relationship for older age groups after accounting for blood pressure. An analysis combing the data for the Prospective Studies Collaboration with data from the Multiple Risk Factors Intervention Trial (MRFIT) also found that lower usual total cholesterol was associated with a lower risk of fatal stroke in those 40 to 49 years of age (HR, 0.87; 95% CI, 0.76 to 1.00 per 1 mmol/L lower total cholesterol), with similar reductions in those 50 to 59 (HR, 0.91; 95% CI, 0.85 to 0.97) and 60 …

Independent Effects of LDL Cholesterol and hsCRP Lowering in the JUPITER Trial

In the 2008 industry-supported JUPITER trial (JW Gen Med Nov 18 2008), healthy people with normal LDL cholesterol levels (<130 mg/dL) and elevated

Statins Reduce the Neurofibrillary Tangle Burden in a Mouse Model of Tauopathy

Statin treatment has been associated with a reduced risk of Alzheimer disease and decreased amyloid deposition in mouse models. No animal studies have reported effects of statins on tau aggregates and neurofibrillary tangles (NFTs), the pathological hallmarks of Alzheimer disease that correlate with dementia. We investigated the effect of statins on NFTs in a transgenic mouse tauopathy model and found the following: 1) 1-month treatment with the blood-brain barrier-permeable agent simvastatin in normocholesterolemic aged mice significantly reduced the NFT burden and decreased lectin-positive microglia; 2) simvastatin significantly decreased NFTs and improved T-maze performance in young animals treated for 8 months; 3) treatment of hypercholesterolemic mice for 5 months with blood-brain barrier-impermeable atorvastatin markedly reduced the NFT burden and decreased lectin-positive microglia; 4) nonstatin cholesterol-lowering strategies showed a modest NFT decrease compared with statin treatment; and 5) there was a positive correlation between microglial and NFT burden (r = 0.8). Together, these results suggest that statins reduce NFT burden irrespective of blood-brain barrier permeability at both early and late ages in long- and short-term treatment paradigms and under normocholesterolemic and hypercholesterolemic conditions. The decrease in microglia, coupled with the limited effect of nonstatin cholesterol lowering, suggests that the anti-NFT effect of statins may be related to their anti-inflammatory and not necessarily to their cholesterol-lowering properties. Statins may provide therapy against NFTs in tauopathies, particularly when NFTs are the major neuropathologic component.

Response to Letter by Mascitelli et al

Response: Dr Mascitelli and colleagues indicate that our exploratory analysis of the relative effects of high dose atorvastatin on secondary stroke prevention in men and women1 did not mention an increased risk of hemorrhagic stroke with treatment. The stroke outcomes included all strokes (ischemic and hemorrhagic). It is not appropriate to perform analyses of subgroups of subgroups.2 Caution must always be used when conducting exploratory analyses.3 In this report, we appropriately tested for statistical interactions between treatment and gender for the SPARCL prespecified primary and secondary end points and found no statistical heterogeneity in the benefit of treatment. In …

The influence of age on the association between cholesterol and cognitive function

With the increasing emphasis on vascular disease as a risk factor for dementia and cognitive impairment, lowering cholesterol has received much attention to maintain cognitive function. Observational studies have shown that high total serum cholesterol levels in middle age, but not in old age, associate with cognitive impairment in later life. This can be explained in part since the association between high levels of total serum cholesterol levels and cardiovascular disease becomes weaker with increasing age and is absent in old age. Most studies on HDL-cholesterol levels show a protective association with cardiovascular disease up to old age, whereas data on the protective association with late-life cognitive impairment is absent. In contrast to general belief, randomized controlled trials and most longitudinal observational studies do not show a positive effect of statin treatment on the risk of dementia when prescribed in later life. In conclusion, high total serum cholesterol in middle age is associated with cognitive impairment and statin therapy is likely to have a benefit on cognitive function via a decrease of cardiovascular pathologies. However, a beneficial effect of cholesterol lowering on cognitive function in old age is uncertain.

A new approach to the treatment of dyslipidemia

During the last decade, the evidence of beneficial effects of cholesterol lowering in patients with coronary heart disease has been proven in many clinical trials. The National Cholesterol Education Program (NCEP) released 2004 update to the Adult Treatment Panel III (ATP III) guidelines. The new guidelines of European Society of Cardiology announced in 2007 support more intensive LDL-C lowering in patients at high risk of cardiovascular diseases. For patients at the highest risk of cardiovascular diseases (diabetic patients with coronary heart disease), the recommended LDL-C goal is <1.8 mmol/L. In very high-, high-, and moderately high-risk patients, statin therapy should be considered with a treatment targeting an LDL-C reduction of 30-40%. Clinical studies have shown that statin therapy alone is not always effective, especially in patients with primary hypercholesterolemia. Furthermore, high doses of statins can increase the possibility of adverse events. The combination of statins with intestinal cholesterol absorption inhibitors is more effective than statin monotherapy in LDL-C lowering and is well tolerated.

Vascular Effects of Diet Supplementation With Plant Sterols

The purpose of this study was to evaluate vascular effects of diet supplementation with plant sterol esters (PSE). Plant sterol esters are used as food supplements to reduce cholesterol levels. Their effects on endothelial function, stroke, or atherogenesis are not known. In mice, plasma sterol concentrations were correlated with endothelial function, cerebral lesion size, and atherosclerosis. Plasma and tissue sterol concentrations were measured by gas-liquid chromatography-mass spectrometry in 82 consecutive patients with aortic stenosis. Compared with those fed with normal chow (NC), wild-type mice fed with NC supplemented with 2% PSE showed increased plant sterol but equal cholesterol plasma concentrations. The PSE supplementation impaired endothelium-dependent vasorelaxation and increased cerebral lesion size after middle cerebral artery occlusion. To test the effects of cholesterol-lowering by PSE, apolipoprotein E (ApoE)-/- mice were randomized to Western-type diet (WTD) with the addition of PSE or ezetimibe (EZE). Compared with WTD, both interventions reduced plaque sizes; however, WTD + PSE showed larger plaques compared with WTD + EZE (20.4 +/- 2.1% vs. 10.0 +/- 1.5%). Plant sterol plasma concentration strongly correlated with increased atherosclerotic lesion formation (r = 0.50). Furthermore, we examined plasma and aortic valve concentrations of plant sterol in 82 consecutive patients with aortic stenosis. Patients eating PSE-supplemented margarine (n = 10) showed increased plasma concentrations and 5-fold higher sterol concentrations in aortic valve tissue. Food supplementation with PSE impairs endothelial function, aggravates ischemic brain injury, effects atherogenesis in mice, and leads to increased tissue sterol concentrations in humans. Therefore, prospective studies are warranted that evaluate not only effects on cholesterol reduction, but also on clinical endpoints.

Randomized trial of the effects of cholesterol-lowering with simvastatin on peripheral vascular and other major vascular outcomes in 20,536 people with peripheral arterial disease and other high-risk conditions

Randomized trial of the effects of cholesterol-lowering with simvastatin on peripheral vascular and other major vascular outcomes in 20,536 people with peripheral arterial disease and other high-risk conditions

Randomized trial of the effects of cholesterol-lowering with simvastatin on peripheral vascular and other major vascular outcomes in 20,536 people with peripheral arterial disease and other high-risk conditions

Randomized trial of the effects of cholesterol-lowering with simvastatin on peripheral vascular and other major vascular outcomes in 20,536 people with peripheral arterial disease and other high-risk conditions

Beneficial effects of aggressive low-density lipoprotein cholesterol lowering in women with stable coronary heart disease in the Treating to New Targets (TNT) study

Objective:To examine by secondary analysis of the Treating to New Targets (TNT) study whether the benefits of intensive versus standard levels of lipid lowering are equally applicable to women.Methods:A total...

Treatment potential for cholesterol management in patients with coronary heart disease in 15 European countries: Findings from the EUROASPIRE II survey

BackgroundDuring the last decade, the evidence of beneficial effects of cholesterol lowering in patients with coronary heart disease (CHD) has been proven in several clinical trials. This has prompted international guidelines on prevention of CHD to include recommendations on dietary and pharmacological treatment of hyperlipidaemia with set goals on total- and LDL-cholesterol. MethodsThe first EUROASPIRE survey performed in 1995/1996 showed poor adherence to the European recommendations on lipid-lowering in patients with CHD. The second survey was carried out in 1999/2000 in 15 European countries and enrolled 8181 patients with CHD. Medical records were assessed and clinical examinations of risk factors including serum lipids were performed. The aim of this survey is to describe the treatment of hyperlipidaemia among CHD patients in Europe. ResultsThe proportion of patients not reaching the target of 5.0mmol/l was 58.3% with significant variations between countries. The use of lipid-lowering drugs was relatively high (60.9%). However, the most frequently used doses of lipid-lowering agents were much lower than the doses of proven effect used in clinical trials. ConclusionsAlthough the treatment of hyperlipidaemia in CHD patients seems to be improving as compared to the first survey, a significant number of patients do not reach treatment goals. If the full potential of lipid-lowering therapy was utilised with all eligible patients treated and doses titrated correctly, more patients would benefit in terms of reduced morbidity and mortality of CHD.

Rationale, design, and baseline characteristics of a randomized trial to assess the effect of cholesterol lowering on the progression of aortic stenosis: The Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) trial

Aortic stenosis (AS) is a common health problem in the western world. Recent studies have suggested that cholesterol lowering may have a salutary effect on the progression of AS. The primary objective of the ASTRONOMER study is to determine whether patients with AS randomized to rosuvastatin will experience less progression in AS severity as measured by aortic transvalvular gradients and valve areas. The secondary objectives are to determine the effect of rosuvastatin on the rate of cardiac death and aortic valve replacement and to assess the time to outcome during a follow-up of 3 to 5 years. This is a double-blind placebo-controlled study. Patients with mild to moderate AS are randomized to receive 40 mg/d of rosuvastatin or placebo. Patients with any clinical indication for the use of cholesterol-lowering agents according to the 2000 Canadian guidelines are excluded. Recruitment of 272 patients from 23 Canadian sites was completed in December 2005. Compared with patients with AS in published trials, the patients in the ASTRONOMER study are younger (58.1 +/- 13.6 years), have less severe AS (AS jet velocity 3.2 +/- 0.4 m/s), and are composed of a great proportion (48.9%) of patients with bicuspid aortic valve. Prevention of the development of severe AS needs to be tested in large randomized studies. Recruitment for the ASTRONOMER trial has been completed and results will be available at the end of 2008.

Invited commentary

Current guidelines give a class I recommendation to lower low-density lipoprotein (LDL) cholesterol levels below 100 mg/dL in all patients with peripheral artery disease (PAD) and a class IIa recommendation to lower the LDL cholesterol level below 70 mg/dL in patients who are at “very high risk of ischemic events.”1Hirsch A.T. Haskal Z.J. Hertzer N.R. et al.ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic).J Am Coll Cardiol. 2006; 47: 1239-1312Abstract Full Text Full Text PDF PubMed Scopus (1068) Google Scholar High-risk PAD would be defined as more than one vascular bed involved—eg, a clinical history of concomitant coronary or cerebral vascular disease. The primary evidence for these recommendations comes from the original publication of the Heart Protection Study that evaluated the benefits of simvastatin in over 20,000 high-risk patients.2MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.Lancet. 2002; 360: 7-22Abstract Full Text Full Text PDF PubMed Scopus (7641) Google Scholar There were 6748 patients with PAD reported in the original publication, and these patients had a reduction in fatal and nonfatal cardiovascular events with simvastatin similar to that in patients with other forms of atherosclerosis. A recent meta-analysis of statin therapy in a broad population of high-risk patients demonstrated that there was a consistent benefit in reduction of risk of cardiovascular events across a wide population of patients and a wide range of baseline LDL cholesterol levels.3Baigent C. Keech A. Kearney P.M. et al.Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.Lancet. 2005; 366: 1267-1278Abstract Full Text Full Text PDF PubMed Scopus (5745) Google Scholar Thus there is a broad consensus to treat all patients at risk with statin drugs, regardless of their baseline cholesterol level. The publication of the Heart Protection Study Collaborative Group in the Journal of Vascular Surgery focuses on the benefits of statin therapy specifically in the PAD population. The major new finding was a significant reduction in noncoronary revascularizations. Confirmatory findings were the consistency of the benefit across all populations studied (including patients with PAD who had no pre-existing coronary artery disease) and benefit regardless of baseline LDL cholesterol level. There was no benefit of the statin in preventing amputations, perhaps reflecting the end-stage pathophysiology of patients who suffer limb loss. The message is clear. All patients with PAD are at high risk and meet criteria for statin therapy. The benefit of statin therapy is primarily systemic (prevention of major cardiovascular events) but also local (reduction of the need for revascularization). Randomized trial of the effects of cholesterol-lowering with simvastatin on peripheral vascular and other major vascular outcomes in 20,536 people with peripheral arterial disease and other high-risk conditionsJournal of Vascular SurgeryVol. 45Issue 4PreviewThe Heart Protection Study (HPS) provides an opportunity to assess directly the effects of cholesterol-lowering therapy on major vascular events (defined as myocardial infarction, coronary death, stroke, or revascularization) in patients with peripheral arterial disease (PAD). In addition, the effects on peripheral vascular events (ie, non-coronary revascularization, aneurysm repairs, major amputations or PAD deaths) can be assessed. Full-Text PDF Open Archive

Randomized trial of the effects of cholesterol-lowering with simvastatin on peripheral vascular and other major vascular outcomes in 20,536 people with peripheral arterial disease and other high-risk conditions

The Heart Protection Study (HPS) provides an opportunity to assess directly the effects of cholesterol-lowering therapy on major vascular events (defined as myocardial infarction, coronary death, stroke, or revascularization) in patients with peripheral arterial disease (PAD). In addition, the effects on peripheral vascular events (ie, non-coronary revascularization, aneurysm repairs, major amputations or PAD deaths) can be assessed. 6748 UK adults with PAD and 13,788 other high-risk participants were randomly allocated to receive 40 mg simvastatin daily or matching placebo, yielding an average LDL cholesterol difference of 1.0 mmol/L (39 mg/dL) during a mean of 5 years. For participants with PAD, allocation to simvastatin was associated with a highly significant 22% (95% CI 15-29) relative reduction in the rate of first major vascular event following randomisation (895 [26.4%] simvastatin-allocated vs 1101 [32.7%] placebo-allocated; P < .0001), which was similar to that seen among the other high-risk participants. The absolute reduction in first major vascular event was 63 (SE 11) per 1000 patients with PAD and 50 (SE 7) per 1000 without pre-existing PAD. Overall, among all participants, there was a 16% (5-25) relative reduction in the rate of first peripheral vascular event following randomisation (479 [4.7%] simvastatin vs 561 [5.5%] placebo), largely irrespective of baseline LDL cholesterol and other factors. This effect chiefly reflects a 20% (8-31) relative reduction in non-coronary revascularization procedures (334 [3.3%] vs 415 [4.0%]; P = .002). HPS demonstrates the benefits of cholesterol-lowering statin therapy in patients with PAD, regardless of their presenting cholesterol levels and other presenting features. Allocation to 40 mg simvastatin daily reduces the rate of first major vascular events by about one-quarter, and that of peripheral vascular events by about one-sixth, with large absolute benefits seen in participants with PAD because of their high vascular risk. Consequently, statin therapy should be considered routinely for all patients with PAD.

Statin Therapy and the Elderly

In the United States, the prevalence of coronary and other cardiovascular diseases increases with age, reflecting in part the cumulative effect of lifetime exposure to cardiovascular risk factors.1 Coronary and cerebrovascular atherosclerosis in the elderly (≥65 years of age) is a growing clinical problem because of the population’s increasing longevity. Despite this evidence, cardiovascular risk in elderly patients is demonstrably undermanaged according to several epidemiological studies.2–4 In a Canadian study, paradoxically, elderly coronary patients who were at the highest risk for recurrent disease appeared to be the least likely to receive preventive treatment.4 Several factors may contribute to this poor level of management, such as confusion surrounding the relevance of certain modifiable risk factors to this age group, the cost-effectiveness of preventing coronary heart disease (CHD) in older patients, and concerns about the impact of therapies on safety and quality of life. Article p 700 Despite early studies that questioned the association of cholesterol with coronary risk in the elderly, the available epidemiology now favors the perspective that cholesterol remains an important modifiable risk factor in patients ≥65 years of age, especially after adjustment for the presence of comorbid conditions.5 Growing evidence demonstrates the benefit of treating higher-risk older patients. In this issue of Circulation , Deedwania et al6 present the results of the Study Assessing Goals in the Elderly (SAGE), which compares the effect of intensive (atorvastatin 80 mg/d) compared with moderate (pravastatin 40 mg/d) cholesterol lowering with statins in a cohort of 893 men and women 65 to 85 years of age with coronary artery disease. SAGE evaluated the absolute change in total duration of ischemia as measured by 48-hour Holter monitoring from baseline to 1 year. Although total ischemia duration was reduced significantly in both arms compared with baseline, the intensive strategy …

Effects of rosuvastatin on 3-nitrotyrosine and aortic stiffness in hypercholesterolemia

Background and aims Early atherosclerosis is characterized by reduced large artery distensibility, paralleled by an increased peroxynitrite formation and nitration of tyrosine in proteins. The aim of the present study was to investigate the short-term effect of cholesterol lowering with rosuvastatin on 3-nitrotyrosine (3-NT), a marker of peroxynitrite-mediated oxidative stress, and on arterial stiffness. Methods and results 71 outpatients with primary hypercholesterolemia were recruited for this randomized open-label intervention study; 35 patients were assigned to 4-week rosuvastatin therapy (10 mg daily) with a low-fat diet, and 36 patients to a low-fat diet only. Within the cohort of 71 hypercholesterolemic patients, there was a significant correlation between cholesterol levels, 3-NT and aortic pulse wave velocity (aPWV), that is a reliable measure of aortic stiffness. Among those patients who received rosuvastatin, significant reductions in plasma cholesterol, 3-NT and aPWV were observed. Reductions in both aPWV and 3-NT levels correlated significantly with the decrease in plasma cholesterol. Reduction of plasma cholesterol was the only independent predictor for reduced arterial stiffness following rosuvastatin therapy. Conclusion Cholesterol reduction achieved following short-term rosuvastatin therapy is associated with a decrease in peroxynitrite-mediated oxidative stress and an improvement in large artery distensibility; reduction in arterial stiffness is directly attributable to rosuvastatin-induced cholesterol lowering and not to reduction of plasma 3-NT levels.