Does aggressive statin therapy offer improved cholesterol-independent benefits compared to conventional statin treatment?

Gupta, Sandeep

doi:10.1016/j.ijcard.2003.10.013

Cited by 12 publications

(6 citation statements)

References 73 publications

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“…The size of the improvement in mortality and the observation that this improvement was also associated with older age at death suggest that cardiovascular risk reduction treatment does prolong survival in this population. The large effect seen in this population is in keeping with previous studies, which suggested that absolute risk reduction is greater in high-risk groups (12- 16,22,23).…”

Section: Statistical Analysessupporting

confidence: 91%

Improved Survival of Diabetic Foot Ulcer Patients 1995–2008

et al. 2008

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OBJECTIVE -The purpose of this study was to determine whether a strategy of aggressive cardiovascular risk management reduced the mortality associated with diabetic foot ulceration. RESEARCH DESIGN AND METHODS-After an initial audit of outcomes demonstrating a high mortality rate in 404 diabetic foot ulcer patients with the first ulceration developing between 1995 and 1999, a new aggressive cardiovascular risk policy was introduced as standard practice at the Diabetic Foot Clinic, Royal Infirmary of Edinburgh, in 2001. In the first 3 years of this policy, 251 patients were screened and identified. The audit cycle was then closed by reauditing the 5-year mortality for this second group of foot ulcer patients in 2008.RESULTS -Overall 5-year mortality was reduced from 48.0% in cohort 1 to 26.8% in cohort 2 (P Ͻ 0.001). Improvement in survival was seen for both neuroischemic patients (5-year mortality of 58% reduced to 36%; relative reduction 38%) and neuropathic patients (36% reduction to 19%; relative reduction 47%) (both P Ͻ 0.001). Patients were more likely to die if they were older at the time of ulceration or had type 2 diabetes, renal impairment, or preexisting cardiovascular disease or were already taking aspirin. Prior statin use, current smoker or exsmoker status, blood pressure, A1C, and total cholesterol were not significantly different between survivors and those who died in the follow-up periods.CONCLUSIONS -Diabetic foot ulcer patients have a high risk of death. Survival has improved over the past 13 years. The adoption of an aggressive cardiovascular risk management policy in diabetic foot ulcer clinics is recommended for these patients. Diabetes Care 31:2143-2147, 2008L ower limb amputation in diabetic patients is associated with significant excess mortality (1). Foot ulceration is also believed to be associated with increased deaths due to related cardiovascular disease (2,3). In addition, patients with foot ulceration often have advanced diabetes complications (4). Cardiovascular risk reduction has, over the last 10 years, become a major part of diabetes care, particularly for type 2 diabetic patients. However, it has only been since 2004 that the U.K. General Medical Services contract has made the treatment of cardiovascular risk a renumerated part of diabetes management in primary care (5). This initiative is driven by target A1C, blood pressure, and cholesterol levels rather than absolute or calculated risk as in the past and has increased prescribing of therapies aimed to reduce cardiovascular risk (6). Patients without established risk factors might not receive adequate treatment if their values are not above the target.It is likely that the peripheral arterial disease and microvascular sclerosis associated with diabetic foot ulceration will reflect established arterial disease elsewhere in the body (3). Therefore, cardiovascular risk factor intervention might be expected to be effective in this setting. However, there are no studies of aggressive risk factor modification in patients with dia...

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Section: Statistical Analysessupporting

confidence: 91%

Improved Survival of Diabetic Foot Ulcer Patients 1995–2008

et al. 2008

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“…Among patients who have recently had acute coronary syndrome, an intensive lipid-lowering statin regimen (80 mg of atorvastatin daily) provides greater protection against death or major cardiovascular events than does a standard regimen (40 mg of pravastatin daily). These findings indicate that such patients benefit from early and continued lowering of LDL-cholesterol to levels substantially below current target levels [37][38][39].…”

Section: Groupsmentioning

confidence: 99%

Beneficial effect of simvastatin and pravastatin treatment on adverse cardiac remodelling and glomeruli loss in spontaneously hypertensive rats

Bezerra

Mandarim-de-Lacerda

2005

Clinical Science

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The aim of the present study was to investigate the possibility of different effects of the hydrophobic statin simvastatin and the hydrophilic statin pravastatin on the remodelling process in the overloaded left ventricle and renal cortex of SHRs (spontaneously hypertensive rats). Fifteen SHRs were treated for 40 days with simvastatin, pravastatin or placebo (water) via orogastric administration. Left ventricle and renal cortex were examined by light microscopy and stereology. LV (left ventricular) cardiomyocyte nuclei (N[cmn]) and glomeruli (N[gl]) numbers were estimated by the dissector method. BP (blood pressure) and serum triacylglycerols (triglycerides) were lower in the statin-treated groups than in the untreated control group. The volume density of the interstitial connective tissue was smaller and length density of the intramyocardial arteries, as well as the arteries/cardiomyocyte ratio, was greater in the statin-treated groups than in the control group. No difference was observed between the two statin-treated groups. The cross-sectional cardiomyocyte area was significantly smaller in the simvastatin-treated group than in the control or pravastatin-treated groups, and it was smaller in the pravastatin-treated group than in the control group. N[cmn] and N[gl] were greater in the two statin-treated groups than in the control group, but no significant difference was observed between the two statin-treated groups. In conclusion, administration of the statins simvastatin and pravastatin to SHRs effectively prevented the elevation in BP and serum triaclyglycerols, and also attenuated adverse cardiac and kidney remodelling by preventing LV hypertrophy, enhancing myocardial vascularization with the decrease in interstitial fibrosis and attenuating cardiomyocyte and glomerular loss.

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“…Long‐term intake of statins has been associated with a decreased prevalence of dementia‐like Alzheimer's disease (AD) in some studies 1–3 . It is of interest to investigate whether this effect is due to reduced cholesterol synthesis in the brain or rather due to possible pleiotrophic effects of statins 4,5 …”

mentioning

confidence: 99%

“…[1][2][3] It is of interest to investigate whether this effect is due to reduced cholesterol synthesis in the brain or rather due to possible pleiotrophic effects of statins. 4,5 In this study, we asked whether high-dose treatment with simvastatin or atorvastatin has an influence on a surrogate marker of brain cholesterol homeostasis, 24(S)-hydroxycholesterol (24S-OH-Chol), in patients with moderately elevated plasma cholesterol levels. 24S-OH-Chol is an oxysterol, which derives exclusively from the brain in humans.…”

mentioning

confidence: 99%

High‐Dose Statin Treatment Does Not Alter Plasma Marker for Brain Cholesterol Metabolism in Patients With Moderately Elevated Plasma Cholesterol Levels

Thelen

Laaksonen

Päivä

et al. 2006

The Journal of Clinical Pharma

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Statins inhibit endogenous cholesterol synthesis, up-regulate low-density lipoprotein (LDL) receptor expression in mammalian liver cells, and thus decrease circulating LDL-cholesterol concentrations. As cholesterol seems to play a role in the development of neurodegenerative diseases, it is of interest to evaluate the effect of high dosages of statins (eg, atorvastatin or simvastatin) on brain cholesterol metabolism. Plasma samples from 44 participants (aged 30-69 years, 16 men and 18 women) of an earlier randomized, placebo-controlled, double-blind trial, who took 40 mg atorvastatin or 80 mg simvastatin daily for 2 months, were used to analyze total cholesterol, its precursor lathosterol, and its metabolites 24(S)-hydroxycholesterol and 27-hydroxycholesterol. Despite a significant decrease in absolute plasma concentrations of oxysterols, total cholesterol, and its endogenous synthesis rate, indicated by a decreased ratio of lathosterol to cholesterol, the plasma 24(S)-hydroxycholesterol to cholesterol ratio, a surrogate marker of brain cholesterol homeostasis, remained unchanged. Short-term high-dose atorvastatin and simvastatin treatment does not seem to influence brain cholesterol metabolism in patients with moderately elevated plasma cholesterol levels.

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Does aggressive statin therapy offer improved cholesterol-independent benefits compared to conventional statin treatment?

Cited by 12 publications

References 73 publications

Improved Survival of Diabetic Foot Ulcer Patients 1995–2008

Improved Survival of Diabetic Foot Ulcer Patients 1995–2008

Beneficial effect of simvastatin and pravastatin treatment on adverse cardiac remodelling and glomeruli loss in spontaneously hypertensive rats

High‐Dose Statin Treatment Does Not Alter Plasma Marker for Brain Cholesterol Metabolism in Patients With Moderately Elevated Plasma Cholesterol Levels

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