| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2000;101:207.)
© 2000 American Heart Association, Inc.
Cardiovascular Drugs |
Current Perspectives on Statins
From the Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University, School of Medicine, Nashville, Tenn.
 |
Abstract |
|---|
Top
Abstract
IntroductionAbstract—Statins (HMG-CoA reductase inhibitors) are used widely for the treatment of hypercholesterolemia. They inhibit HMG-CoA reductase competitively, reduce LDL levels more than other cholesterol-lowering drugs, and lower triglyceride levels in hypertriglyceridemic patients. Statins are well tolerated and have an excellent safety record. Clinical trials in patients with and without coronary heart disease and with and without high cholesterol have demonstrated consistently that statins reduce the relative risk of major coronary events by
30% and produce a greater absolute
benefit in patients with higher baseline risk. Proposed mechanisms
include favorable effects on plasma lipoproteins,
endothelial function, plaque architecture and
stability, thrombosis, and inflammation. Mechanisms independent of LDL
lowering may play an important role in the clinical benefits conferred
by these drugs and may ultimately broaden their indication from
lipid-lowering to antiatherogenic agents.
Key Words: statins • hypercholesterolemia • trials • atherosclerosis • coronary disease
|
Introduction |
|---|
The advent of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins, has revolutionized the treatment of hypercholesterolemia. Statins are the most commonly prescribed agents for the treatment of hypercholesterolemia because of their efficacy in reducing LDL and their excellent tolerability and safety. This review examines the pharmacology, clinical trials, and proposed mechanisms of clinical benefits of statins.
|
Mechanism of Action |
|---|
Statins competitively inhibit HMG-CoA reductase, the enzyme that catalyzes the rate-limiting step in cholesterol biosynthesis.1 The resultant reduction in hepatocyte cholesterol concentration triggers increased expression of hepatic LDL receptors, which clear LDL and LDL precursors from the circulation.2 Statins may inhibit hepatic synthesis of apolipoprotein B-100 and decrease the synthesis and secretion of triglyceride-rich lipoproteins.3 4 Although the primary mechanism of action for LDL lowering is enhanced clearance of LDL via LDL receptors, reduced hepatic production and secretion of lipoproteins may explain the observation that atorvastatin and simvastatin are capable of lowering LDL in patients with homozygous familial hypercholesterolemia who have no functional LDL receptors.5 6
|
Pharmacology |
|---|
Lovastatin, pravastatin, and simvastatin are derived from fungal fermentation. Fluvastatin, atorvastatin, and cerivastatin are entirely synthetic. Lovastatin, simvastatin, atorvastatin, and cerivastatin utilize the cytochrome P 450 (CYP) 3A4 pathway for metabolism or biotransformation.7 Fluvastatin metabolism occurs via CYP2C9, and pravastatin does not use the CYP pathway significantly.8 Pravastatin is extremely hydrophilic compared with other statins except for fluvastatin, which has intermediate physicochemical properties. This difference in hydrophilicity has not been demonstrated to have clinical significance.
|
Effects on Plasma Lipids and Lipoproteins |
|---|
Statins are highly effective in reducing LDL and modestly effective in raising HDL. Triglyceride lowering is directly proportional to the baseline triglyceride level and to the LDL-lowering potency of the drug.9 10
Table 1
shows the comparative
efficacy and potency of statins on lipids and lipoproteins in patients
without hypertriglyceridemia. In general,
LDL is reduced an additional 7% with each doubling of the
dose.11 Statins do not lower lipoprotein(a) [Lp(a)]
concentration.16 Statins are also ineffective in modifying
the size and density of LDL.17
|
|
Adverse Effects |
|---|
As a class, statins are well tolerated, and there are no known differences in safety. The most important adverse effects are liver and muscle toxicity. The incidence of transaminase increases greater than 3-fold is
1% for all statins and is dose
related.18 19 20 21 22 If this occurs, the drug should be stopped;
transaminase levels generally return to baseline within 2 to 3
months.19
The major adverse effect of statins is myopathy, defined as muscle pain
or weakness associated with creatine kinase (CK) levels higher than 10
times the upper limit of normal. Myopathy with statin monotherapy
occurs in 1 in 1000 patients and is dose related. Symptoms may
include fever and malaise, and cases have been associated with elevated
serum statin drug levels. Rhabdomyolysis and acute renal failure may
result if myopathy is not recognized and the drug is
continued.23 If recognized promptly and the drug is
stopped, the myopathy is reversible, and acute renal failure is
unlikely to ensue.
The combination of statins with certain drugs that are CYP3A4 inhibitors or substrates increases the risk of myopathy, presumably by inhibiting the metabolism of the statin and increasing its blood concentration. These drugs include cyclosporine,24 erythromycin,7 clarithromycin,7 nefazodone,7 azole antifungals,7 protease inhibitors, and mibefradil (with lovastatin and simvastatin).25 Fibrates and niacin also increase the risk of statin-induced myopathy via a mechanism that does not increase plasma statin concentrations.26 Myopathy has been reported with pravastatin even though pravastatin is not metabolized significantly by CYP.27 Statins with and without CYP metabolism have been used safely in low doses in combination with cyclosporine in heart transplant patients.28 29 Other risk factors for statin-induced myopathy are hepatic dysfunction, renal insufficiency, hypothyroidism, advanced age, and serious infection.
Monitoring for Liver and Muscle Toxicity
Both baseline and periodic monitoring of liver transaminases are
recommended. Baseline measurement of CK may be useful. Small,
clinically insignificant increases in transaminases and CK are commonly
observed with all statins.12 Routine follow-up CK
measurements are generally not recommended, because severe myopathy
usually occurs suddenly and is not preceded by chronic elevations of
CK.4 Patients should be instructed to contact their
physician if they experience muscle pain or weakness, severe malaise,
or flulike symptoms. If this occurs, statin therapy should be
discontinued, and the CK level should be measured without delay. Many
experts would consider rechallenge with a different statin after the CK
level returns to normal, beginning with a low dose and monitoring
closely for symptoms and elevated CK.
|
Combination With Other Lipid-Lowering Drugs |
|---|
The combination of statins with other lipid-lowering medications is sometimes necessary to achieve recommended target lipoprotein levels. The combination of a statin with a bile acid–binding resin is highly effective for LDL lowering, because these drugs work via different mechanisms to stimulate LDL receptor clearance of LDL.2 On occasion, triple therapy with statin, resin, and niacin is required to achieve satisfactory LDL control. Although the addition of a statin to gemfibrozil or niacin increases the risk of myopathy, statins administered in low doses have been found to be safe in combination with fibrates30 and with niacin.31 Combination drug therapy associated with increased risk of myopathy should not be given unless the indication is compelling (coronary heart disease [CHD] or other high-risk condition) and the patient is reliable and fully informed of the possible side effects. The efficacy of statin-fibrate or statin-niacin combination on clinical events is not known.
|
Clinical Trials |
|---|
Secondary-Prevention Studies
The secondary-prevention trials are summarized in Table 2
. The Scandinavian
Simvastatin Survival Study (4S) demonstrated a convincing
reduction in total mortality among the subjects in the
simvastatin group.15 The reduction in
coronary events in 4S was observed in both men and women, in
individuals younger and older than 60 years of age, and in subjects
with other risk factors, including smoking, hypertension, and
diabetes.32 In addition, 4S reported a 30% reduction in
cerebrovascular events.
|
The Cholesterol And Recurrent Events (CARE) study extended the findings of 4S to individuals with average cholesterol levels.21 Post hoc analysis revealed no reduction in coronary events among patients in the treatment group with baseline LDL levels below 125 mg/dL, which led the authors to suggest that statin treatment of CHD patients with low LDL levels may not be warranted. Diabetic subjects treated with pravastatin (n=282) had a 25% reduction in major coronary events compared with diabetic subjects taking placebo.21
The Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study extended the findings of CARE by including subjects with unstable angina and by using CHD death as the primary end point, which was reduced by 24% in the pravastatin group.33
Primary-Prevention Studies
The primary-prevention trials are summarized in Table 2
.
The West of Scotland Coronary Prevention Study (WOSCOPS) found a
significant reduction in the primary end point of coronary
death and nonfatal myocardial infarction after 5 years.20
Because of the lower baseline risk in the WOSCOPS population, the
number needed to treat (NNT) to prevent 1 major coronary event
(NNT=100/absolute risk reduction) was higher (NNT=42) than that found
in 4S (NNT=15), CARE (NNT=33), or LIPID (NNT=28). In a subgroup
analysis, high-risk individuals (>2% event rate per
year) were those younger than 55 years of age and with vascular
disease, smoking, or minor ECG abnormalities, or older
hypercholesterolemic individuals with any additional
risk factor.34 If treatment had been focused on these
high-risk individuals, the NNT would have been reduced from 42 to
17.
The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) found that lovastatin prevented first acute major coronary events in men and women with average LDL levels and low HDL levels.22 Individuals in the 2 lowest HDL tertiles (HDL <40 mg/dL) benefited the most. This study raises the question of whether the position of the National Cholesterol Education Program (NCEP) should be altered to recommend statin treatment in patients whose risk profile includes HDL <40 mg/dL.
Effects of Statins on Cerebrovascular and Peripheral
Vascular Disease
Analysis of 45 prospective observational cohorts that
reported 13 397 strokes in 450 000 people demonstrated no independent
association of baseline total cholesterol level and risk of
stroke, except perhaps in individuals younger than 45 years of
age.35 Two meta-analyses found
secondary-prevention trials produced a significant reduction in
cerebrovascular events, whereas primary prevention resulted in a
nonsignificant reduction in stroke rate.36 37 Trials that
used serial B-mode carotid ultrasound in patients with and without CHD
showed that statins slow progression and induce regression of carotid
atherosclerosis.38 39
Although pravastatin did not affect femoral atherosclerosis in a primary-prevention setting,39 it significantly reduced the intima-media thickness of the common femoral artery in subjects with coronary artery disease.39A Simvastatin was also shown to be beneficial in intermittent claudication.40
Angiographic Trials
Statins slow the progression and induce the regression of
coronary atherosclerosis, reduce the formation
of new lesions, and reduce the incidence of coronary
events.41 Although the absolute change in
arterial narrowing is relatively small, the frequency of
cardiovascular events is decreased substantially in
most of these studies. This apparent disparity between the small degree
of angiographic change and the relatively large differences in clinical
event rates led to the concept of plaque stabilization and a profound
change in our understanding of the biology of the atherosclerotic
plaque.42
|
Mechanisms for Clinical Benefits |
|---|
Effects on Endothelial Function
Hypercholesterolemia reduces endothelial production and increases degradation of nitric oxide (NO).43 Cholesterol lowering by statins44 45 results in significant improvement in endothelial function. Both pravastatin and lovastatin significantly reduce the frequency and intensity of ischemic episodes as detected by 48-hour Holter monitoring after as little as 4 months of therapy.46 47 The effects of statins on endothelial function may be partially independent of cholesterol lowering. Both simvastatin and lovastatin induce transcriptional activation of the NO synthase gene in human endothelial cells in vitro.48 Endothelial function improves in primates receiving a dose of pravastatin that does not reduce LDL.49 Furthermore, both simvastatin and lovastatin exert a dose-dependent protective effect in an experimental stroke model, mediated by increased production of endothelial NO synthase rather than cholesterol lowering.50
Another relevant observation comes from 4S and CARE, in which simvastatin and pravastatin reduced LDL to different degrees (35% and 28%, respectively) with different effects on major coronary events (32% versus 23% reduction, respectively), yet the effect on stroke and transient ischemic attack was similar (28% and 31% reduction, respectively).15 21 These observations argue in favor of a direct, non–LDL-mediated effect of statins on endothelial function.
Effects on the Cellular Components of Atherosclerotic
Plaque
Statins can decrease smooth muscle cell growth in vitro at
pharmacological doses.51 Additionally, both
simvastatin and pravastatin reduce the
proliferation of macrophages induced by oxidized LDL in vitro
and reduce the accumulation of cholesteryl esters in
macrophages exposed to oxidized LDL.52 53 It is
well established that statins inhibit the growth of lymphocytes and
other blood mononuclear cells via multiple pathways unrelated to
cholesterol metabolism,54 55 an
effect whose therapeutic relevance is currently being investigated in
patients with leukemia.56
Effects on Thrombosis and Inflammation
Statins may affect thrombus formation, erythrocyte deformability,
and levels of plasminogen activator
inhibitor-1 and fibrinogen, with possible substantial
differences among the different molecules.57 A recent
subanalysis of the CARE trial58 showed that
pravastatin lowers the levels of C-reactive protein and
eliminates the higher risk of cardiovascular events
associated with this inflammatory marker. Pravastatin also
reduced the incidence of organ rejection and the cytotoxicity of
natural killer cells in recipients of heart28 and
kidney59 transplants.
|
Unresolved Questions |
|---|
Correlation Between Degree of Cholesterol Lowering and Clinical Benefits
The significant clinical benefits observed in the large clinical trials with statins could be due entirely to the reduction in LDL. Several facts support this position. First, the clinical effects of treatment in 4S (simvastatin lowered LDL by 35%) were much stronger than those observed in CARE (pravastatin lowered LDL by 28%).15 21 Second, the Post Coronary Artery Bypass Graft (Post CABG) demonstrated that the aggressive reduction of LDL with lovastatin (to
95 mg/dL) produced better
angiographic outcomes and reduced the rate of
revascularization procedures compared with a more
moderate LDL reduction (to 135 mg/dL).60 Also, the
magnitude of benefit obtained in these major trials is comparable to
that reported in the Program On Surgical Control of
Hyperlipidemia (POSCH), in which ileal bypass was used
to produce a 37% reduction in LDL levels.61
However, attributing the different clinical results in 4S and
CARE simply to different degrees of LDL lowering may be misleading
because of the much lower baseline LDL level in the CARE subjects and
the consequently much higher baseline risk of CHD recurrences
and death in the 4S subjects. In fact, when a group of >500 CARE
subjects was selected for enrollment characteristics similar to those
of the 4S inclusion criteria (higher LDL and higher risk), the effect
of pravastatin on clinical outcomes was similar to that of
simvastatin, despite a 10 percentage-point smaller
reduction in LDL produced in the CARE subjects compared with 4S
subjects.21 Additionally, the better angiographic results
obtained by aggressive treatment of LDL in the Post CABG study did not
translate into reduction in coronary events or death. Finally,
no significant effects on event rates were detected in the first 4
years of POSCH, which suggests that the anatomic changes induced on the
plaque by a substantial cholesterol reduction take 
5
years to translate into clinical benefits.
The nature of the correlation between the extent of cholesterol reduction with statins and the degree of clinical benefit is controversial. Post hoc analyses of the WOSCOPS, CARE, and 4S studies have resulted in conflicting reports. In WOSCOPS, the reduction in the rate of fatal and nonfatal CHD was related to LDL lowering up to a 24% level, but no additional benefits were observed for reductions in LDL as great as 39%.61A Similarly, the relative risk of an end point in CARE was progressively reduced with LDL levels declining from 140 to 120 mg/dL, but additional lowering of LDL did not produce additional risk reduction.62 On the other hand, the relationship between cholesterol reduction and event reduction in 4S was curvilinear and never reached a threshold.63
Although apparently divergent, these results could be a function of
global risk and the baseline LDL level in the populations studied
(Figure). The benefit of LDL
lowering may be limited by the risk imposed by other factors unrelated
to LDL. Thus, the shape of the correlation curve may be mostly a
function of the baseline risk in the population studied. If this
interpretation is correct, one can postulate that a moderate reduction
in LDL (25%) will produce maximum benefits in moderate-risk
populations, whereas more aggressive reductions in LDL to the levels
recommended by the NCEP guidelines or beyond would produce additional
benefits in high-risk hypercholesterolemic
populations.64
|
|
Clinical Recommendations |
|---|
Patients With Atherosclerosis
It is now accepted as a standard of care to lower LDL to <100 mg/dL in patients with atherosclerosis. Given the relatively small number of CHD patients with untreated LDL below this level and poor physician compliance with NCEP guidelines, and considering that non-LDL effects of statins may confer additional protection, the use of statins in all patients with atherosclerosis should be considered. Treatment in these patients should be initiated at the earliest opportunity, such as the time of diagnosis of an acute coronary or cerebrovascular event.
Patients With Diabetes
The risk of a major coronary event is as high in diabetic
subjects without known CHD as in nondiabetic survivors of myocardial
infarction.65 Data from both 4S and CARE show that the
absolute risk reduction induced by statin treatment was larger in
diabetic than in nondiabetic subjects.21 32 For this
reason, LDL lowering is now recognized as the first priority in the
control of diabetic dyslipidemia,66 and statin
treatment should be implemented in the majority of type 2 diabetic
patients with LDL >100 mg/dL.
Asymptomatic Patients With Multiple Risk
Factors
Statin therapy should be prioritized according to the patient’s
global risk. It is evident that among asymptomatic
individuals, the absolute benefit of therapy with statins is greatest
for subjects with the highest baseline risk. If the level of absolute
risk deserving aggressive intervention is 2% per
year,67 and the expected risk reduction by statin
treatment is 30%, then the target NNT in practice would be 33 over
5 years or lower. Along this line of thinking, statins may be seen as
antiatherogenic agents that will affect overall CHD risk even when the
LDL level is not the most prominent problem within the risk
profile.
Patients With Moderate
Hypertriglyceridemia or Combined
Hyperlipidemia
A recent consensus statement advocates the use of statins as
first-line treatment in high-risk patients with
triglyceride levels below 500 mg/dL.4 The
combination of low-dose statin with nicotinic acid or fibrates for
combined hyperlipidemia is a safe approach when
performed with appropriate monitoring and after careful patient
education.68 Statins are not appropriate first-line
therapy in individuals with severe
hypertriglyceridemia.
Patients With Low HDL
Data from 4S,69 CARE,21 and
AFCAPS/TexCAPS22 show impressive clinical benefits in
subgroups with low levels of HDL. These results suggest that statin
treatment may be appropriate for patients with low HDL levels not
simply because of the LDL lowering and direct arterial wall
effects, but possibly because of the increase in HDL. Given the
combined effect of statins on LDL and HDL, it is reasonable to use the
ratio of total cholesterol to HDL, as recommended by the
Canadian guidelines,70 with a goal of <5 in high-risk and
<4 in very-high-risk individuals.
|
Future Directions |
|---|
Within the next few years, we will learn whether statins produce a benefit in the setting of acute coronary syndromes and how statin therapy, alone or as a major component of medical therapy, compares with revascularization procedures for patients with stable coronary disease. Indeed, a recent trial71 found that high-dose atorvastatin was at least as effective as angioplasty plus usual care in reducing coronary events in patients with stable CHD. Another important area of inquiry will be the evaluation of statin therapy in the prevention of stroke in subjects at high risk for cerebrovascular events.
Although statins are cost-effective in high-risk groups,72 they are vastly underutilized among patients with coronary disease.73 It is critically important that practices become organized so that high-risk patients are systematically identified and treated. Risk assessment is equally important to identify patients at the lower end of the risk spectrum, when the cost of statin therapy may not be justified.
Our understanding of the pharmacological effects of statins is evolving toward the realization that these agents do more than simply lower cholesterol. Similar to the ACE inhibitors, whose role as antihypertensive agents is now surpassed by their effects on cardiac and renal function, statins may produce benefits both by decreasing cholesterol and by lipid-independent mechanisms, and they are poised to become invaluable tools in the prevention and management of CHD.
|
Acknowledgments |
|---|
Drs Fazio and Linton are Established Investigators of the American Heart Association and are supported by American Heart Association Grants-in-Aid 95011450 and 9750728 and by National Institutes of Health grants HL-57986 and HL-53989.
|
Footnotes |
|---|
Address correspondence to any of the authors at Vanderbilt University School of Medicine, 315 Medical Research Building II, Nashville, TN 37232-6300.
|
References |
|---|
1. Endo A, Tsujita Y, Kuroda M, Tanzawa K. Inhibition of cholesterol synthesis in vitro and in vivo by ML-236A and ML-236B, competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Eur J Biochem. 1977;77:31–36.
2. Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis. Science. 1986;232:34–47.
3. Ginsberg HN, Le NA, Short MP, Ramakrishnan R, Desnick RJ. Suppression of apolipoprotein B production during treatment of cholesteryl ester storage disease with lovastatin: implications for regulation of apolipoprotein B synthesis. J Clin Invest. 1987;80:1692–1697.
4. Grundy SM. Consensus statement: role of therapy with "statins" in patients with hypertriglyceridemia. Am J Cardiol. 1998;81(suppl 4A):1B–6B.
5. Marais AD, Naoumova RP, Firth JC, Penny C, Neuwirth CK, Thompson GR. Decreased production of low density lipoprotein by atorvastatin after apheresis in homozygous familial hypercholesterolemia. J Lipid Res. 1997;38:2071–2078.
6. Raal FJ, Pilcher GJ, Illingworth DR, Pappu AS, Stein EA, Laskarzewski P, Mitchel YB, Melino MR. Expanded dose simvastatin is effective in homozygous familial hypercholesterolemia. Atherosclerosis. 1997;135:249–256.
7. Anonymous. Choice of lipid-lowering drugs. Med Lett Drugs Ther. 1998;40:117–122.
8. Lennernas H, Fager G. Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors: similarities and differences. Clin Pharmacokinet. 1997;32:403–425.
9. Bakker-Arkema RG, Davidson MH, Goldstein RJ, Davignon J, Isaacsohn JL, Weiss SR, Keilson LM, Brown WV, Miller VT, Shurzinske LJ, Black DM. Efficacy and safety of a new HMG-CoA reductase inhibitor, atorvastatin, in patients with hypertriglyceridemia. JAMA. 1996;275:128–133.
10. Stein EA, Lane M, Laskarzewski P. Comparison of statins in hypertriglyceridemia. Am J Cardiol. 1998;81:66B–69B.
11. Roberts WC. The rule of 5 and the rule of 7 in lipid-lowering by statin drugs. Am J Cardiol. 1997;82:106–107.
12. Illingworth DR, Tobert JA. A review of clinical trials comparing HMG-CoA reductase inhibitors. Clin Ther. 1994;16:366–385.
13. Jones P, Kafonek S, Laurora I, Hunninghake D. Comparative dose efficacy study of atorvastatin versus simvastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study). Am J Cardiol. 1998;81:582–587.
14. Stein E. Cerivastatin in primary hyperlipidemia: a multicenter analysis of efficacy and safety. Am J Cardiol. 1998;82:40J–46J.
15. Stein EA, Davidson MH, Dobs AS, Schrott H, Dujovne CA, Bays H, Weiss SR, Melino MR, Stepanavage ME, Mitchel YB. Efficacy and safety of simvastatin 80 mg/day in hypercholesterolemic patients. Am J Cardiol. 1998;82:311–316. [
16. Kostner GM, Gavish D, Leopold B, Bolzano K, Weintraub MS, Breslow JL. HMG-CoA reductase inhibitors lower LDL cholesterol without reducing Lp(a) levels. Circulation. 1989;80:1313–1319.
17. Bredie SJ, de Bruin TW, Demacker PN, Kastelein JJ, Stalenhoef AF. Comparison of gemfibrozil versus simvastatin in familial combined hyperlipidemia and effects on apolipoprotein-B-containing lipoproteins, low-density lipoprotein subfraction profile, and low-density lipoprotein oxidizability. Am J Cardiol. 1995;75:348–353. [
18. The Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383–1389.
19. Bradford RH, Shear CL, Chremos AN, Dujovne C, Downton M, Franklin FA, Gould AL, Hesney M, Higgins J, Hurley DP, Langendorfer A, Nash DT, Pool JL, Schnaper H. Expanded clinical evaluation of lovastatin (EXCEL) study results, I: efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia. Arch Intern Med. 1991;151:43–49.
20. Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, Macfarlane PW, McKillop JH, Packard CJ. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med. 1995;333:1301–1307.
21. Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, Brown L, Warnica JW, Arnold JM, Wun CC, Davis BR, Braunwald E. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med. 1996;335:1001–1009.
22. Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, Langendorfer A, Stein EA, Kruger W, Gotto AJ. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. JAMA. 1998;279:1615–1622.
23. Pierce LR, Wysowski DK, Gross TP. Myopathy and rhabdomyolysis associated with lovastatin-gemfibrozil combination therapy. JAMA. 1990;264:71–75.
24. Norman DJ, Illingworth DR, Munson J, Hosenpud J. Myolysis and acute renal failure in a heart-transplant recipient receiving lovastatin. N Engl J Med. 1988;318:46–47.
25. Food and Drug Administration. Warning Labeling Changes for the New Heart Drug Posicor. Rockville, Md: National Press Office; December 19, 1997. Talk Paper T97–65.
26. Gruer PJK, Vega JM, Mercuri MF, Dobrinska M, Tobert JA. Concomitant use of cytochrome p450 3A4 inhibitors and simvastatin. Am J Cardiol. 1999;84:811–815.
27. Haria M, McTavish D. Pravastatin: a reappraisal of its pharmacological properties and clinical effectiveness in the management of coronary heart disease. Drugs. 1997;53:299–336.
28. Kobashigawa JA, Katznelson S, Laks H, Johnson JA, Yeatman L, Wang XM, Chia D, Terasaki PI, Sabad A, Cogert GA, Trosian K, Hamilton MA, Moriguchi JD, Kawata N, Habe A, Drinkwater DC, Stevenson LW. Effect of pravastatin on outcomes after cardiac transplantation. N Engl J Med. 1995;333:621–627.
29. Wenke K, Meiser B, Thiery J, Nagel D, von Scheidt W, Steinbeck G, Seidel D, Reichart B. Simvastatin reduces graft vessel disease and mortality after heart transplantation: a four-year randomized trial. Circulation. 1997;96:1398–1402.
30. Wiklund O, Angelin B, Bergman M, Berglund L, Bondjers G, Carlsson A, Linden T, Miettinen T, Ödman B, Olofsson S-O, Saarinen I, Sipilä R, Sjöström P, Kron B, Vanhanen H, Wright I. Pravastatin and gemfibrozil alone and in combination for the treatment of hypercholesterolemia. Am J Med. 1993;94:13–20.
31. Stein E, Davidson MH, Dujovne CA, Hunninghake DB, Goldberg RB, Illingworth DR, Knopp RH, Miller VT, Frost P, Isaacsohn JL, Mitchel YB, Melino MR, Shapiro D, Tobert JA. Efficacy and tolerability of low-dose simvastatin and niacin, alone and in combination, in patients with combined hyperlipidemia: a prospective trial. J Cardiovasc Pharmacol Ther. 1996;1:107–116.
32. Pyorala K, Pedersen TR, Kjekshus J, Faergeman O, Olsson AG, Thorgeirsson G, for the Scandinavian Simvastatin Survival Study Group. Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease. Diabetes Care. 1997;20:614–620.
33. The Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998;339:1349–1357.
34. Anonymous. West of Scotland Coronary Prevention Study: identification of high-risk groups and comparison with other cardiovascular intervention trials. Lancet. 1996;348:1339–1342.
35. Prospective Studies Collaboration. Cholesterol, diastolic blood pressure, and stroke: 13 000 strokes in 450 000 people in 45 prospective cohorts. Lancet. 1995;346:1647–1653.
36. Crouse JR, Byington RP, Hoen HM, Furberg CD. Reductase inhibitor monotherapy and stroke prevention. Arch Intern Med. 1997;157:1305–1310.
37. Hebert PR, Gaziano JM, Chan KS, Hennekens CH. Cholesterol lowering with statin drugs, risk of stroke, and total mortality. JAMA. 1997;278:313–321.
38. Furberg CD, Adams HPJ, Applegate WB, Byington RP, Espeland MA, Hartwell T, Hunninghake DB, Lefkowitz DS, Probstfield J, Riley WA, Young B, for the Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group. Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Circulation. 1994;90:1679–1687.
39. Salonen R, Nyyssonen K, Porkkala E, Rummukainen J, Belder R, Park JS, Salonen JT. Kuopio Atherosclerosis Prevention Study (KAPS): a population-based primary preventive trial of the effect of LDL lowering on atherosclerotic progression in carotid and femoral arteries. Circulation. 1995;92:1758–1764.
39. de Groot E, Jukema JW, Montauban van Swijndregt AD, Zwinderman AH, Ackerstaff RG, van der Steen AF, Bom N, Lie KI, Bruschke AV. B-mode ultrasound assessment of pravastatin treatment effect on carotid and femoral artery walls and its correlations with coronary arteriographic findings: a report of the Regression Growth Evaluation Statin Study (REGRESS). J Am Coll Cardiol.. 1998;31:1561–1567.
40. Pedersen TR, Kjekshus J, Pyorala K, Olsson AG, Cook TJ, Musliner TA, Tobert JA, Haghfelt T. Effect of simvastatin on ischemic signs and symptoms in the Scandinavian Simvastatin Survival Study (4S). Am J Cardiol. 1998;81:333–335.
41. Ballantyne CM, Herd JA, Dunn JK, Jones PH, Farmer JA, Gotto AMJ. Effects of lipid lowering therapy on progression of coronary and carotid artery disease. Curr Opin Lipidol. 1997;8:354–361.
42. Brown BG, Zhao X-Q. Importance of endothelial function in mediating the benefits of lipid-lowering therapy. Am J Cardiol. 1998;82:49T–52T.
43. Ludmer PL, Selwyn AP, Shook TL, Wayne RR, Mudge GH, Alexander RW, Ganz P. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med. 1986;315:1046–1051.
44. Anderson TJ, Meredith IT, Yeung AC, Frei B, Selwyn AP, Ganz P. The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion. N Engl J Med. 1995;332:488–493.
45. Treasure CB, Klein JL, Weintraub WS, Talley JD, Stillabower ME, Kosinski AS, Zhang J, Boccuzzi SJ, Cedarholm JC, Alexander RW. Beneficial effects of cholesterol-lowering therapy on the coronary endothelium in patients with coronary artery disease. N Engl J Med. 1995;332:481–487.
46. van Boven AJ, Jukema JW, Zwinderman AH, Crijns HJ, Lie KI, Bruschke AV. Reduction of transient myocardial ischemia with pravastatin in addition to the conventional treatment in patients with angina pectoris. Circulation. 1996;94:1503–1505.
47. Andrews TC, Raby K, Barry J, Naimi CL, Allred E, Ganz P, Selwyn AP. Effect of cholesterol reduction on myocardial ischemia in patients with coronary disease. Circulation. 1997;95:324–328.
48. Laufs U, Fata VL, Plutzky J, Liao JK. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation. 1998;97:1129–1135.
49. Williams JK, Sukhova GK, Herrington DM, Libby P. Pravastatin has cholesterol-lowering independent effects on the artery wall of atherosclerotic monkeys. J Am Coll Cardiol. 1998;31:684–691.
50. Endres M, Laufs U, Huang Z, Nakamura T, Huang P, Moskowitz MA, Liao JK. Stroke protection by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase. Proc Natl Acad Sci U S A. 1998;95:8880–8885.
51. Negre-Aminoux P, van Vliet AK, van Erck M, van Thiel GC, van Leeuwen RE, Cohen LH. Inhibition of proliferation of human smooth muscle cells by various HMG-CoA reductase inhibitors: comparison with other human cell types. Biochim Biophys Acta. 1997;1345:259–268.
52. Kempen HJM, Vermeer M, deWit E, Havekes LM. Vastatins inhibit cholesterol ester accumulation in human monocyte-derived macrophages. Arterioscler Thromb. 1991;11:146–153.
53. Sakai M, Kobori S, Matsumura T, Biwa T, Sato Y, Takemura T, Hakamata H, Horiuchi S, Shichiri M. HMG-CoA reductase inhibitors suppress macrophage growth induced by oxidized low density lipoprotein. Atherosclerosis. 1997;133:51–59.
54. Tatsuno I, Tanaka T, Oeda T, Yasuda T, Kitagawa M, Saito Y, Hirai A. Geranylgeranylpyrophosphate, a metabolite of mevalonate, regulates the cell cycle progression and DNA synthesis in human lymphocytes. Biochem Biophys Res Commun. 1997;241:376–382.
55. Hirai A, Nakamura S, Noguchi Y, Yasuda T, Kitagawa M, Tatsuno I, Oeda T, Tahara K, Terano T, Narumiya S, Kohn LD, Saito Y. Geranylgeranylated Rho small GTPase(s) are essential for the degradation of p27 kip1 and facilitate the progression from G1 to S phase in growth-stimulated rat FRTL-5 cells. J Biol Chem. 1997;272:13–16.
56. Newman A, Clutterbuck RD, Powles RL, Catovsky D, Millar JL. A comparison of the effect of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors simvastatin, lovastatin, and pravastatin on leukaemic and normal bone marrow progenitors. Leuk Lymphoma. 1997;24:533–537.
57. Rosenson RS, Tangney CC. Antiatherothrombotic properties of statins: implications for cardiovascular event reduction. JAMA. 1998;279:1643–1650.
58. Ridker PM, Rifai N, Pfeffer MA, Sacks F, Braunwald E. Long-term effects of pravastatin on plasma concentration of C-reactive protein. Circulation. 1999;100:230–235.
59. Katznelson S, Wilkinson AH, Kobashigawa JA, Wang X-M, Chia D, Ozawa M, Zhong H-P, Hirata M, Cohen AH, Terasaki PI, Danovitch GM. The effect of pravastatin on acute rejection after kidney transplantation: a pilot study. Transplantation. 1996;61:1469–1474.
60. The Post Coronary Artery Bypass Graft Trial Investigators. The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary-artery bypass grafts. N Engl J Med. 1997;336:153–162.
61. Buchwald H, Varco RL, Matts JP, Long JM, Fitch LL, Campbell GS, Pearce MB, Yellin AE, Edmiston WA, Smink RD Jr, Sawin HS Jr, Campos CT, Hansen BJ, Tuna N, Karnegis JN, Sanmarco ME, Amplatz K, Castaneda-Zuniga WR, Hunter DW, Bissett JK, Weber FJ, Stevenson JW, Leon AS, Chalmers TC, for the POSCH Group. Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia: report of the Program on the Surgical Control of the Hyperlipidemias (POSCH). N Engl J Med. 1990;323:946–955.
61. West of Scotland Coronary Prevention Study Group. Influence of pravastatin and plasma lipids on clinical events in the West of Scotland Coronary Prevention Study (WOSCOPS). Circulation.. 1998;97:1440–1445.
62. Sacks FM, Moye LA, Davis BR, Cole TG, Rouleau JL, Nash DT, Pfeffer MA, Braunwald E. Relationship between plasma LDL concentrations during treatment with pravastatin and recurrent coronary events in the Cholesterol And Recurrent Events trial. Circulation. 1998;97:1446–1452.
63. Pedersen TR, Olsson AG, Faergeman O, Kjekshus J, Wedel H, Berg K, Wilhelmsen L, Haghfelt T, Thorgeirsson G, Pyorala K, Miettinen T, Christophersen B, Tobert JA, Musliner TA, Cook TJ. Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S). Circulation. 1998;97:1453–1460.
64. Fazio S, Linton MF. On the relationship between cholesterol reduction and coronary disease event rate. Circulation. 1998;98:2645–2646. Letter.
65. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229–234.
66. American Diabetes Association. Management of dyslipidemia in adults with diabetes (Position Statement). Diabetes Care. 1999;22(suppl 1):S56–S59.
67. Pyorala K, Baker GD, Graham I, Poole-Wilson P, Wood D. Prevention of coronary heart disease in clinical practice: recommendations of the task force of the European Society of Cardiology, European Atherosclerosis Society and European Society of Hypertension. Eur Heart J. 1994;15:1300–1331.
68. Tikkanen MJ. Statins: within-group comparisons, statin escape and combination therapy. Curr Opin Lipidol. 1996;7:385–388.
69. The Scandinavian Simvastatin Survival Study Group. Baseline serum cholesterol and treatment effect in the Scandinavian Simvastatin Survival Study. Lancet. 1995;345:1724–1725.
70. Frohlich J, Fodor G, McPherson R, Genest J, Langner N. Rationale for and outline of the recommendations of the Working Group on Hypercholesterolemia and Other Dyslipidemias: interim report. Can J Cardiol. 1998;14(suppl A):17–21.
71. Pitt B, Waters D, Brown WV, van Boven AJ, Schwartz L, Title LM, Eisenberg D, Shurzinske L, McCormick LS. Aggressive lipid-lowering therapy compared with angioplasty in stable coronary artery disease. N Engl J Med. 1999;341:70–76.
72. Jacobson TA, Schein JR, Williamson A, Ballantyne CM. Maximizing the cost-effectiveness of lipid-lowering therapy. Arch Intern Med. 1998;158:1977–1989.
73. Pearson TA, Laurora IM. Attainment of LDL-cholesterol goals in a national sample: results from the Lipid Treatment Assessment Project (L-TAP). J Am Coll Cardiol. 1998;31:88A. Abstract.
This article has been cited by other articles:
 |
|
 |
|
  J. Lightwood, K. Bibbins-Domingo, P. Coxson, Y. C. Wang, L. Williams, and L. Goldman Forecasting the Future Economic Burden of Current Adolescent Overweight: An Estimate of the Coronary Heart Disease Policy Model Am J Public Health, December 1, 2009; 99(12): 2230 - 2237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. L. S. Brookes, C. C. McGown, and C. S. Reilly Statins for all: the new premed? Br. J. Anaesth., July 1, 2009; 103(1): 99 - 107. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Maeda and N. Horiuchi Simvastatin Suppresses Leptin Expression in 3T3-L1 Adipocytes via Activation of the Cyclic AMP-PKA Pathway Induced by Inhibition of Protein Prenylation J. Biochem., June 1, 2009; 145(6): 771 - 781. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. T. Denton, M. Kurt, N. D. Shah, S. C. Bryant, and S. A. Smith Optimizing the Start Time of Statin Therapy for Patients with Diabetes Med Decis Making, May 1, 2009; 29(3): 351 - 367. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Schlitt, S. Blankenberg, C. Bickel, K. J. Lackner, G. H. Heine, M. Buerke, K. Werdan, L. Maegdefessel, U. Raaz, H. J. Rupprecht, et al. PLTP activity is a risk factor for subsequent cardiovascular events in CAD patients under statin therapy: the AtheroGene Study J. Lipid Res., April 1, 2009; 50(4): 723 - 729. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Pletcher, L. Lazar, K. Bibbins-Domingo, A. Moran, N. Rodondi, P. Coxson, J. Lightwood, L. Williams, and L. Goldman Comparing Impact and Cost-Effectiveness of Primary Prevention Strategies for Lipid-Lowering Ann Intern Med, February 17, 2009; 150(4): 243 - 254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Gottsater, D. Flondell-Site, T. Kolbel, and B. Lindblad Associations Between Statin Treatment and Markers of Inflammation, Vasoconstriction, and Coagulation in Patients With Abdominal Aortic Aneurysm Vascular and Endovascular Surgery, January 1, 2009; 42(6): 567 - 573. [Abstract] [PDF]
|
|
|
|
 |
|
 N. Isma, J. Barani, I. Mattiasson, B. Lindblad, and A. Gottsater Lipid-Lowering Therapy is Related to Inflammatory Markers and 3-Year Mortality in Patients With Critical Limb Ischemia Angiology, October 1, 2008; 59(5): 542 - 548. [Abstract] [PDF]
|
|
|
|
 |
|
 L. G. Mikael and R. Rozen Homocysteine modulates the effect of simvastatin on expression of ApoA-I and NF-{kappa}B/iNOS Cardiovasc Res, October 1, 2008; 80(1): 151 - 158. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Waksman, P. E. McEwan, T. I. Moore, R. Pakala, F. D. Kolodgie, D. G. Hellinga, R. C. Seabron, S. J. Rychnovsky, J. Vasek, R. W. Scott, et al. PhotoPoint Photodynamic Therapy Promotes Stabilization of Atherosclerotic Plaques and Inhibits Plaque Progression J. Am. Coll. Cardiol., September 16, 2008; 52(12): 1024 - 1032. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Gao, W. Wang, and I. H. Zucker Simvastatin Inhibits Central Sympathetic Outflow in Heart Failure by a Nitric-Oxide Synthase Mechanism J. Pharmacol. Exp. Ther., July 1, 2008; 326(1): 278 - 285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Loppnow, K. Werdan, and M. Buerke Invited review: Vascular cells contribute to atherosclerosis by cytokine- and innate-immunity-related inflammatory mechanisms Innate Immunity, April 1, 2008; 14(2): 63 - 87. [Abstract] [PDF]
|
|
|
|
 |
|
 M. M. Elahi, F. R. Cagampang, F. W. Anthony, N. Curzen, S. K. Ohri, and M. A. Hanson Statin Treatment in Hypercholesterolemic Pregnant Mice Reduces Cardiovascular Risk Factors in Their Offspring Hypertension, April 1, 2008; 51(4): 939 - 944. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yamashita, F. Otsuka, T. Mukai, H. Otani, K. Inagaki, T. Miyoshi, J. Goto, M. Yamamura, and H. Makino Simvastatin antagonizes tumor necrosis factor-{alpha} inhibition of bone morphogenetic proteins-2-induced osteoblast differentiation by regulating Smad signaling and Ras/Rho-mitogen-activated protein kinase pathway J. Endocrinol., March 1, 2008; 196(3): 601 - 613. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Gao, L. Linhartova, A. McD. Johnston, and D. R. Thickett Statins and sepsis Br. J. Anaesth., March 1, 2008; 100(3): 288 - 298. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-H. Hsieh, S.-F. Jeng, M.-W. Hsieh, Y.-C. Chen, C.-S. Rau, T.-H. Lu, and S.-S. Chen Statin-Induced Heme Oxygenase-1 Increases NF-{kappa}B Activation and Oxygen Radical Production in Cultured Neuronal Cells Exposed to Lipopolysaccharide Toxicol. Sci., March 1, 2008; 102(1): 150 - 159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-H. Hsieh, C.-S. Rau, M.-W. Hsieh, Y.-C. Chen, S.-F. Jeng, T.-H. Lu, and S.-S. Chen Simvastatin-Induced Heme Oxygenase-1 Increases Apoptosis of Neuro 2A Cells in Response to Glucose Deprivation Toxicol. Sci., January 1, 2008; 101(1): 112 - 121. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Villagra, N. Ulloa, X. Zhang, Z. Yuan, E. Sotomayor, and E. Seto Histone Deacetylase 3 Down-regulates Cholesterol Synthesis through Repression of Lanosterol Synthase Gene Expression J. Biol. Chem., December 7, 2007; 282(49): 35457 - 35470. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Rosengarten, D. Auch, and M. Kaps Effects of Initiation and Acute Withdrawal of Statins on the Neurovascular Coupling Mechanism in Healthy, Normocholesterolemic Humans Stroke, December 1, 2007; 38(12): 3193 - 3197. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. D. Flick, L. A. Habel, K. A. Chan, S. K. Van Den Eeden, V. P. Quinn, R. Haque, E. J. Orav, J. D. Seeger, M. C. Sadler, C. P. Quesenberry Jr., et al. Statin Use and Risk of Prostate Cancer in the California Men's Health Study Cohort Cancer Epidemiol. Biomarkers Prev., November 1, 2007; 16(11): 2218 - 2225. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Blanco, F. Nombela, M. Castellanos, M. Rodriguez-Yanez, M. Garcia-Gil, R. Leira, I. Lizasoain, J. Serena, J. Vivancos, M. A. Moro, et al. Statin treatment withdrawal in ischemic stroke: A controlled randomized study Neurology, August 28, 2007; 69(9): 904 - 910. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Momin, N. Melikian, S. B. Wheatcroft, D. Grieve, L. C. John, A. El Gamel, M. T. Marrinan, J. B. Desai, C. Driver, R. Sherwood, et al. The association between saphenous vein endothelial function, systemic inflammation, and statin therapy in patients undergoing coronary artery bypass surgery J. Thorac. Cardiovasc. Surg., August 1, 2007; 134(2): 335 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. S. Packard, S. Schlegel, D. Senouf, F. Burger, P. Sigaud, T. Perneger, C.-A. Siegrist, and F. Mach Atorvastatin Treatment and Vaccination Efficacy J. Clin. Pharmacol., August 1, 2007; 47(8): 1022 - 1027. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bulhak, J. Roy, U. Hedin, P.-O. Sjoquist, and J. Pernow Cardioprotective effect of rosuvastatin in vivo is dependent on inhibition of geranylgeranyl pyrophosphate and altered RhoA membrane translocation Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H3158 - H3163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. J. Frost, H. Petersen, K. Tollestrup, and B. Skipper Influenza and COPD Mortality Protection as Pleiotropic, Dose-Dependent Effects of Statins Chest, April 1, 2007; 131(4): 1006 - 1012. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Hauck, C. Harms, D. Grothe, J. An, K. Gertz, G. Kronenberg, R. Dietz, M. Endres, and R. von Harsdorf Critical Role for FoxO3a-Dependent Regulation of p21CIP1/WAF1 in Response to Statin Signaling in Cardiac Myocytes Circ. Res., January 5, 2007; 100(1): 50 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Nakata, M. Tsutsui, H. Shimokawa, T. Yamashita, A. Tanimoto, H. Tasaki, K. Ozumi, K. Sabanai, T. Morishita, O. Suda, et al. Statin Treatment Upregulates Vascular Neuronal Nitric Oxide Synthase Through Akt/NF-{kappa}B Pathway Arterioscler Thromb Vasc Biol, January 1, 2007; 27(1): 92 - 98. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Davidson, J. M. McKenney, C. L. Shear, and J. H. Revkin Efficacy and Safety of Torcetrapib, a Novel Cholesteryl Ester Transfer Protein Inhibitor, in Individuals With Below-Average High-Density Lipoprotein Cholesterol Levels J. Am. Coll. Cardiol., November 7, 2006; 48(9): 1774 - 1781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. McKenney, M. H. Davidson, C. L. Shear, and J. H. Revkin Efficacy and Safety of Torcetrapib, a Novel Cholesteryl Ester Transfer Protein Inhibitor, in Individuals With Below-Average High-Density Lipoprotein Cholesterol Levels on a Background of Atorvastatin J. Am. Coll. Cardiol., November 7, 2006; 48(9): 1782 - 1790. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Umeji, S. Umemoto, S. Itoh, M. Tanaka, S. Kawahara, T. Fukai, and M. Matsuzaki Comparative effects of pitavastatin and probucol on oxidative stress, Cu/Zn superoxide dismutase, PPAR-{gamma}, and aortic stiffness in hypercholesterolemia Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2522 - H2532. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Hulten, J. L. Jackson, K. Douglas, S. George, and T. C. Villines The Effect of Early, Intensive Statin Therapy on Acute Coronary Syndrome: A Meta-analysis of Randomized Controlled Trials. Arch Intern Med, September 25, 2006; 166(17): 1814 - 1821. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Writing Committee Members, V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: full text: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society Europace, September 1, 2006; 8(9): 651 - 745. [Full Text] [PDF]
|
|
|
|
|
|
V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society J. Am. Coll. Cardiol., August 15, 2006; 48(4): e149 - e246. [Full Text] [PDF]
|
|
|
|
 |
|
 V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society Circulation, August 15, 2006; 114(7): e257 - e354. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Otterdal, C. Smith, E. Oie, T. M. Pedersen, A. Yndestad, E. Stang, K. Endresen, N. O. Solum, P. Aukrust, and J. K. Damas Platelet-derived LIGHT induces inflammatory responses in endothelial cells and monocytes Blood, August 1, 2006; 108(3): 928 - 935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Douglas, P. G. O'Malley, and J. L. Jackson Meta-Analysis: The Effect of Statins on Albuminuria Ann Intern Med, July 18, 2006; 145(2): 117 - 124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Alves-Filho and F. Q. Cunha Modulation of toll-like receptor expression: a further effect of statins? Arterioscler Thromb Vasc Biol, July 1, 2006; 26(7): e128 - e128. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ohkita, M. Sugii, Y. Ka, A. Kitamura, T. Mori, T. Hayashi, M. Takaoka, and Y. Matsumura Differential Effects of Different Statins on Endothelin-1 Gene Expression and Endothelial NOS Phosphorylation in Porcine Aortic Endothelial Cells. Experimental Biology and Medicine, June 1, 2006; 231(6): 772 - 776. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Suzuki, M. Saito, T. Nagai, H. Saeki, and Y. Kazatani Prevention of Positive Coronary Artery Remodeling with Statin Therapy in Patients with Coronary Artery Diseases Angiology, May 1, 2006; 57(3): 259 - 265. [Abstract] [PDF]
|
|
|
|
 |
|
 W. R. Coward, A. Marei, A. Yang, M. M. Vasa-Nicotera, and S. C. Chow Statin-Induced Proinflammatory Response in Mitogen-Activated Peripheral Blood Mononuclear Cells through the Activation of Caspase-1 and IL-18 Secretion in Monocytes J. Immunol., May 1, 2006; 176(9): 5284 - 5292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Watanabe, S. Sugiyama, K. Kugiyama, O. Honda, H. Fukushima, H. Koga, Y. Horibata, T. Hirai, T. Sakamoto, M. Yoshimura, et al. Stabilization of Carotid Atheroma Assessed by Quantitative Ultrasound Analysis in Nonhypercholesterolemic Patients With Coronary Artery Disease J. Am. Coll. Cardiol., December 6, 2005; 46(11): 2022 - 2030. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ohashi, H. Mu, X. Wang, Q. Yao, and C. Chen Reverse cholesterol transport and cholesterol efflux in atherosclerosis QJM, December 1, 2005; 98(12): 845 - 856. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Tousoulis, C. Antoniades, C. Vassiliadou, M. Toutouza, C. Pitsavos, C. Tentolouris, A. Trikas, and C. Stefanadis Effects of combined administration of low dose atorvastatin and vitamin E on inflammatory markers and endothelial function in patients with heart failure Eur J Heart Fail, December 1, 2005; 7(7): 1126 - 1132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Jaschke, C. Michaelis, S. Milz, M. Vogeser, T. Mund, L. Hengst, A. Kastrati, A. Schomig, and R. Wessely Local statin therapy differentially interferes with smooth muscle and endothelial cell proliferation and reduces neointima on a drug-eluting stent platform Cardiovasc Res, December 1, 2005; 68(3): 483 - 492. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zhang, Z. G. Zhang, G. L. Ding, Q. Jiang, X. Liu, H. Meng, A. Hozeska, C. Zhang, L. Li, D. Morris, et al. Multitargeted Effects of Statin-Enhanced Thrombolytic Therapy for Stroke With Recombinant Human Tissue-Type Plasminogen Activator in the Rat Circulation, November 29, 2005; 112(22): 3486 - 3494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Murata, K. Kinoshita, M. Hori, M. Kuwahara, H. Tsubone, H. Karaki, and H. Ozaki Statin Protects Endothelial Nitric Oxide Synthase Activity in Hypoxia-Induced Pulmonary Hypertension Arterioscler Thromb Vasc Biol, November 1, 2005; 25(11): 2335 - 2342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D.M. Engelmann and J. H. Svendsen Inflammation in the genesis and perpetuation of atrial fibrillation Eur. Heart J., October 2, 2005; 26(20): 2083 - 2092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Chan, R. L Hui, and E. Levin Differential Association Between Statin Exposure and Elevated Levels of Creatine Kinase Ann. Pharmacother., October 1, 2005; 39(10): 1611 - 1615. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Erkkila, M. Jauhiainen, K. Laitinen, K. Haasio, T. Tiirola, P. Saikku, and M. Leinonen Effect of Simvastatin, an Established Lipid-Lowering Drug, on Pulmonary Chlamydia pneumoniae Infection in Mice Antimicrob. Agents Chemother., September 1, 2005; 49(9): 3959 - 3962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yamakuchi, J. J.M. Greer, S. J. Cameron, K. Matsushita, C. N. Morrell, K. Talbot-Fox, W. M. Baldwin III, D. J. Lefer, and C. J. Lowenstein HMG-CoA Reductase Inhibitors Inhibit Endothelial Exocytosis and Decrease Myocardial Infarct Size Circ. Res., June 10, 2005; 96(11): 1185 - 1192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. S. Ali and K. J. Buth Preoperative statin use and in-hospital outcomes following heart surgery in patients with unstable angina Eur. J. Cardiothorac. Surg., June 1, 2005; 27(6): 1051 - 1056. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Kennedy, C. D. MacLean, B. Littenberg, P. A. Ades, and R. G. Pinckney The Challenge of Achieving National Cholesterol Goals in Patients With Diabetes Diabetes Care, May 1, 2005; 28(5): 1029 - 1034. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. N. Kao Simvastatin Treatment of Pulmonary Hypertension: An Observational Case Series Chest, April 1, 2005; 127(4): 1446 - 1452. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Watts, E. M. Sampson, G. S. Schultz, and M. A. Spiteri Simvastatin Inhibits Growth Factor Expression and Modulates Profibrogenic Markers in Lung Fibroblasts Am. J. Respir. Cell Mol. Biol., April 1, 2005; 32(4): 290 - 300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E C Jury and M R Ehrenstein Statins: immunomodulators for autoimmune rheumatic disease? Lupus, March 1, 2005; 14(3): 192 - 196. [Abstract] [PDF]
|
|
|
|
|
|
K. Sakamoto, T. Murata, H. Chuma, M. Hori, and H. Ozaki Fluvastatin Prevents Vascular Hyperplasia by Inhibiting Phenotype Modulation and Proliferation Through Extracellular Signal-Regulated Kinase 1 and 2 and p38 Mitogen-Activated Protein Kinase Inactivation in Organ-Cultured Artery Arterioscler Thromb Vasc Biol, February 1, 2005; 25(2): 327 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Leon, B. A. Franklin, F. Costa, G. J. Balady, K. A. Berra, K. J. Stewart, P. D. Thompson, M. A. Williams, and M. S. Lauer Cardiac Rehabilitation and Secondary Prevention of Coronary Heart Disease: An American Heart Association Scientific Statement From the Council on Clinical Cardiology (Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity), in Collaboration With the American Association of Cardiovascular and Pulmonary Rehabilitation Circulation, January 25, 2005; 111(3): 369 - 376. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Watts and M. A. Spiteri Connective tissue growth factor expression and induction by transforming growth factor-{beta} is abrogated by simvastatin via a Rho signaling mechanism Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1323 - L1332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. K. Shetty, P. A. Economides, E. S. Horton, C. S. Mantzoros, and A. Veves Circulating Adiponectin and Resistin Levels in Relation to Metabolic Factors, Inflammatory Markers, and Vascular Reactivity in Diabetic Patients and Subjects at Risk for Diabetes Diabetes Care, October 1, 2004; 27(10): 2450 - 2457. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A K Mantel-Teeuwisse, W G Goettsch, O H Klungel, A de Boer, and R M C Herings Long term persistence with statin treatment in daily medical practice Heart, September 1, 2004; 90(9): 1065 - 1066. [Full Text] [PDF]
|
|
|
|
|
|
C. J. Vaughan and A. M. Gotto Jr Update on Statins: 2003 Circulation, August 17, 2004; 110(7): 886 - 892. [Full Text] [PDF]
|
|
|
|
 |
|
 L. Zeng, H. Xu, T.-L. Chew, R. Chisholm, M. M. Sadeghi, Y. S. Kanwar, and F. R. Danesh Simvastatin Modulates Angiotensin II Signaling Pathway by Preventing Rac1-Mediated Upregulation of p27 J. Am. Soc. Nephrol., July 1, 2004; 15(7): 1711 - 1720. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Kluft Identifying patients at risk of coronary vascular disease: the potential role of inflammatory markers Eur. Heart J. Suppl., July 1, 2004; 6(suppl_C): C21 - C27. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Matsumoto, D. Einhaus, E. S. Gold, and A. Aderem Simvastatin Augments Lipopolysaccharide-Induced Proinflammatory Responses in Macrophages by Differential Regulation of the c-Fos and c-Jun Transcription Factors J. Immunol., June 15, 2004; 172(12): 7377 - 7384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sata, H. Nishimatsu, J.-i. Osuga, K. Tanaka, N. Ishizaka, S. Ishibashi, Y. Hirata, and R. Nagai Statins Augment Collateral Growth in Response to Ischemia but They Do Not Promote Cancer and Atherosclerosis Hypertension, June 1, 2004; 43(6): 1214 - 1220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Mach Statins as Immunomodulatory Agents Circulation, June 1, 2004; 109(21_suppl_1): II-15 - II-17. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Waehre, A. Yndestad, C. Smith, T. Haug, S. H. Tunheim, L. Gullestad, S. S. Froland, A. G. Semb, P. Aukrust, and J. K. Damas Increased Expression of Interleukin-1 in Coronary Artery Disease With Downregulatory Effects of HMG-CoA Reductase Inhibitors Circulation, April 27, 2004; 109(16): 1966 - 1972. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Blanco-Colio, J. L. Martin-Ventura, J. M. Sol, C. Diaz, G. Hernandez, and J. Egido Decreased circulating Fas ligand in patients with familial combined hyperlipidemia or carotid atherosclerosis: Normalization by atorvastatin J. Am. Coll. Cardiol., April 7, 2004; 43(7): 1188 - 1194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Haendeler, J. Hoffmann, J. F. Diehl, M. Vasa, I. Spyridopoulos, A. M. Zeiher, and S. Dimmeler Antioxidants Inhibit Nuclear Export of Telomerase Reverse Transcriptase and Delay Replicative Senescence of Endothelial Cells Circ. Res., April 2, 2004; 94(6): 768 - 775. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Tambaki, E. Rizos, V. Tsimihodimos, A. D. Tselepis, and M. Elisaf Effects of Antihypertensive and Hypolipidemic Drugs on Plasma and High-Density Lipoprotein-Associated Platelet Activating Factor-Acetylhydrolase Activity Journal of Cardiovascular Pharmacology and Therapeutics, April 1, 2004; 9(2): 91 - 95. [Abstract] [PDF]
|
|
|
|
|
|
A J. Kahri, M. M Valkonen, M. K. Vuoristo, and P. J Pentikainen Rhabdomyolysis associated with concomitant use of simvastatin and clarithromycin Ann. Pharmacother., April 1, 2004; 38(4): 719 - 719. [Full Text] [PDF]
|
|
|
|
|
|
K. Kumagai, H. Nakashima, and K. Saku The HMG-CoA reductase inhibitor atorvastatin prevents atrial fibrillation by inhibiting inflammation in a canine sterile pericarditis model Cardiovasc Res, April 1, 2004; 62(1): 105 - 111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Economides, A. Caselli, E. Tiani, L. Khaodhiar, E. S. Horton, and A. Veves The Effects of Atorvastatin on Endothelial Function in Diabetic Patients and Subjects at Risk for Type 2 Diabetes J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 740 - 747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. N. Singh Survival Advantage with Cardiovascular Drugs: Are they Real? Journal of Cardiovascular Pharmacology and Therapeutics, December 1, 2003; 8(4): 249 - 251. [PDF]
|
|
|
|
|
|
K. Shimizu, M. Aikawa, K. Takayama, P. Libby, and R. N. Mitchell Direct Anti-Inflammatory Mechanisms Contribute to Attenuation of Experimental Allograft Arteriosclerosis by Statins Circulation, October 28, 2003; 108(17): 2113 - 2120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Johnston and J. D. Easton Are Patients With Acutely Recovered Cerebral Ischemia More Unstable? Stroke, October 1, 2003; 34(10): 2446 - 2450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nishimura, L. T. Vaszar, J. L. Faul, G. Zhao, G. J. Berry, L. Shi, D. Qiu, G. Benson, R. G. Pearl, and P. N. Kao Simvastatin Rescues Rats From Fatal Pulmonary Hypertension by Inducing Apoptosis of Neointimal Smooth Muscle Cells Circulation, September 30, 2003; 108(13): 1640 - 1645. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Nangle, M. A. Cotter, and N. E. Cameron Effects of Rosuvastatin on Nitric Oxide-Dependent Function in Aorta and Corpus Cavernosum of Diabetic Mice: Relationship to Cholesterol Biosynthesis Pathway Inhibition and Lipid Lowering Diabetes, September 1, 2003; 52(9): 2396 - 2402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Mulhaupt, C. M Matter, B. R Kwak, G. Pelli, N. R Veillard, F. Burger, P. Graber, T. F Luscher, and F. Mach Statins (HMG-CoA reductase inhibitors) reduce CD40 expression in human vascular cells Cardiovasc Res, September 1, 2003; 59(3): 755 - 766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S van Wissen, T J Smilde, M D Trip, T. de Boo, J J P Kastelein, and A F H Stalenhoef Long term statin treatment reduces lipoprotein(a) concentrations in heterozygous familial hypercholesterolaemia Heart, August 1, 2003; 89(8): 893 - 896. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Bruckert, P. Giral, and P. Tellier Perspectives in Cholesterol-Lowering Therapy: The Role of Ezetimibe, a New Selective Inhibitor of Intestinal Cholesterol Absorption Circulation, July 1, 2003; 107(25): 3124 - 3128. [Full Text] [PDF]
|
|
|
|
|
|
P. E. Szmitko, P. W.M. Fedak, R. D. Weisel, D. J. Stewart, M. J.B. Kutryk, and S. Verma Endothelial Progenitor Cells: New Hope for a Broken Heart Circulation, June 24, 2003; 107(24): 3093 - 3100. [Full Text] [PDF]
|
|
|
|
|
|
Z. S. Tan, S. Seshadri, A. Beiser, P. W. F. Wilson, D. P. Kiel, M. Tocco, R. B. D'Agostino, and P. A. Wolf Plasma Total Cholesterol Level as a Risk Factor for Alzheimer Disease: The Framingham Study Arch Intern Med, May 12, 2003; 163(9): 1053 - 1057. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Waehre, J. K. Damas, L. Gullestad, A. M. Holm, T. R. Pedersen, K. E. Arnesen, H. Torsvik, S. S. Froland, A. G. Semb, and P.a. Aukrust Hydroxymethylglutaryl coenzyme a reductase inhibitors down-regulate chemokines and chemokine receptors in patients with coronary artery disease J. Am. Coll. Cardiol., May 7, 2003; 41(9): 1460 - 1467. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Wilson, A. R. Chade, A. Feldstein, T. Sawamura, C. Napoli, A. Lerman, and L. O. Lerman Lipid-lowering-independent effects of simvastatin on the kidney in experimental hypercholesterolaemia Nephrol. Dial. Transplant., April 1, 2003; 18(4): 703 - 709. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-C. Corvol, A. Bouzamondo, M. Sirol, J.-S. Hulot, P. Sanchez, and P. Lechat Differential Effects of Lipid-Lowering Therapies on Stroke Prevention: A Meta-analysis of Randomized Trials Arch Intern Med, March 24, 2003; 163(6): 669 - 676. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Aktas, S. Waiczies, A. Smorodchenko, J. Dorr, B. Seeger, T. Prozorovski, S. Sallach, M. Endres, S. Brocke, R. Nitsch, et al. Treatment of Relapsing Paralysis in Experimental Encephalomyelitis by Targeting Th1 Cells through Atorvastatin J. Exp. Med., March 17, 2003; 197(6): 725 - 733. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Ballantyne, A. Corsini, M. H. Davidson, H. Holdaas, T. A. Jacobson, E. Leitersdorf, W. Marz, J. P. D. Reckless, and E. A. Stein Risk for Myopathy With Statin Therapy in High-Risk Patients Arch Intern Med, March 10, 2003; 163(5): 553 - 564. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Maeda, T. Kawane, and N. Horiuchi Statins Augment Vascular Endothelial Growth Factor Expression in Osteoblastic Cells via Inhibition of Protein Prenylation Endocrinology, February 1, 2003; 144(2): 681 - 692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Gertz, U. Laufs, U. Lindauer, G. Nickenig, M. Bohm, U. Dirnagl, and M. Endres Withdrawal of Statin Treatment Abrogates Stroke Protection in Mice Stroke, February 1, 2003; 34(2): 551 - 557. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Majlesi, P. Samorapoompichit, A. W. Hauswirth, G.-H. Schernthaner, M. Ghannadan, M. Baghestanian, A. Rezaie-Majd, R. Valenta, W. R. Sperr, H.-J. Buhring, et al. Cerivastatin and atorvastatin inhibit IL-3-dependent differentiation and IgE-mediated histamine release in human basophils and downmodulate expression of the basophil-activation antigen CD203c/E-NPP3 J. Leukoc. Biol., January 1, 2003; 73(1): 107 - 117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. W. Chan, A. M. Oza, and L. L. Siu The Statins as Anticancer Agents Clin. Cancer Res., January 1, 2003; 9(1): 10 - 19. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Dichtl, J. Dulak, M. Frick, H. F. Alber, S. P. Schwarzacher, M. P.S. Ares, J. Nilsson, O. Pachinger, and F. Weidinger HMG-CoA Reductase Inhibitors Regulate Inflammatory Transcription Factors in Human Endothelial and Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, January 1, 2003; 23(1): 58 - 63. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Schachinger and A. M. Zeiher Atherogenesis--recent insights into basic mechanisms and their clinical impact Nephrol. Dial. Transplant., December 1, 2002; 17(12): 2055 - 2064. [Full Text] [PDF]
|
|
|
|
|
|
R. Breitling and S. K. Krisans A second gene for peroxisomal HMG-CoA reductase? A genomic reassessment J. Lipid Res., December 1, 2002; 43(12): 2031 - 2036. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nishimura, J. L. Faul, G. J. Berry, L. T. Vaszar, D. Qiu, R. G. Pearl, and P. N. Kao Simvastatin Attenuates Smooth Muscle Neointimal Proliferation and Pulmonary Hypertension in Rats Am. J. Respir. Crit. Care Med., November 15, 2002; 166(10): 1403 - 1408. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||