Primary prevention with statins for older adults

Ryan, Aidan; Heath, Simon; Cook, Paul

doi:10.1136/bmj.k3695

Cited by 5 publications

(4 citation statements)

References 14 publications

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“…In view of the paucity of definite evidence, considering and discussing patient preference might play a relevant role …”

Section: Clues To Optimal Treatment Choicementioning

confidence: 99%

“…In view of the paucity of definite evidence, considering and discussing patient preference might play a relevant role. 85,94 Obviously, statin treatment in extremely frail and disabled patients, end-stage dementia patients or in the end-of-life period is not justified. 95 We need to underline that this tentative approach is largely empirical, and might benefit from direct validation.…”

Section: Assessment Of Frailtymentioning

confidence: 99%

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Management of high cholesterol levels in older people

Bertolotti

Lancellotti

Mussi

2019

Geriatrics Gerontology Int

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The management of hypercholesterolemia in older adults still represents a challenge in clinical medicine. The pathophysiological alterations of cholesterol metabolism associated with aging are still incompletely understood, even if epidemiological evidence suggests that serum cholesterol levels increase with ongoing age, possibly with a plateau after the age of 80 years. Age is also one of the main determinants of cardiovascular disease, according to all cardiovascular risk estimate tools. Cholesterol‐lowering treatment, therefore, would be expected to bring significant protection, even in these patients. Unfortunately, direct experimental evidence is extremely limited, particularly in the very old age strata of the population; a clinical benefit still seems to be present, but the risk for drug‐related adverse events is clearly higher. At any rate, at the present time, definite guidelines for the correct management of hypercholesterolemia in older patients are not available. Therefore, the decision whether or not a pharmacological treatment should be set up, and the choice of the drug, need to be tailored to the individual patient, and requires accurate clinical judgment. The specific aspects of frailty and disability, along with the actual age of the patients, have to be considered together, with a comprehensive assessment approach. The present review summarizes the evidence regarding the modifications of cholesterol metabolism in older patients, the impact of lipid‐lowering drugs on cardiovascular outcomes and focuses on the considerations that can help to define the most appropriate treatment strategy, in view of the individual functional profile. Geriatr Gerontol Int 2019; 19: 375–383.

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“…In view of the paucity of definite evidence, considering and discussing patient preference might play a relevant role …”

Section: Clues To Optimal Treatment Choicementioning

confidence: 99%

Section: Assessment Of Frailtymentioning

confidence: 99%

Management of high cholesterol levels in older people

Bertolotti

Lancellotti

Mussi

2019

Geriatrics Gerontology Int

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“…Statins are widely used to lower plasma cholesterol levels. They inhibit the mevalonate pathway that mediates cholesterol synthesis ( 2 , 3 , 4 ). While use of statins effectively reduces the risk of atherosclerotic events, several studies have demonstrated that statin treatment may have adverse effects including myotoxicity, impaired insulin sensitivity and increased risk for type 2 diabetes ( 6 , 12 , 14 , 32 ).…”

Section: Discussionmentioning

confidence: 99%

“…HMG-CoA reductase inhibitors, statins, lower cholesterol levels by inhibiting mevalonate formation, the rate-limiting step in the cholesterol biosynthesis ( 1 ). These drugs are widely used and effective in primary ( 2 , 3 ) and secondary ( 4 ) prevention of atherosclerotic events. However, data from several clinical studies have demonstrated that statin treatment increases the risk of type 2 diabetes ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Simvastatin profoundly impairs energy metabolism in primary human muscle cells

Mäkinen

Datta

Nguyen

et al. 2020

Endocrine Connections

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Objectives: Simvastatin use is associated with muscular side effects, and increased risk for type 2 diabetes (T2D). In clinical use, simvastatin is administered in inactive lipophilic lactone-form, which is then converted to active acid-form in the body. Here, we have investigated if lactone- and acid-form simvastatin differentially affect glucose metabolism and mitochondrial respiration in primary human skeletal muscle cells. Methods: Muscle cells were exposed separately to lactone- and acid-form simvastatin for 48 h. After pre-exposure, glucose uptake and glycogen synthesis were measured using radioactive tracers; insulin signalling was detected with western blotting; and glycolysis, mitochondrial oxygen consumption and ATP production were measured with Seahorse XFe96 analyzer. Results: Lactone-form simvastatin increased glucose uptake and glycogen synthesis, whereas acid-form simvastatin did not affect glucose uptake and decreased glycogen synthesis. Phosphorylation of insulin signalling targets Akt substrate 160 kDa (AS160) and glycogen synthase kinase 3β (GSK3β) was upregulated with lactone-, but not with acid-form simvastatin. Exposure to both forms of simvastatin led to a decrease in glycolysis and glycolytic capacity, as well as to a decrease in mitochondrial respiration and ATP production. Conclusions: These data suggest that lactone- and acid-forms of simvastatin exhibit differential effects on non-oxidative glucose metabolism as lactone-form increases and acid-form impairs glucose storage into glycogen, suggesting impaired insulin sensitivity in response to acid-form simvastatin. Both forms profoundly impair oxidative glucose metabolism and energy production in human skeletal muscle cells. These effects may contribute to muscular side effects and risk for T2D observed with simvastatin use.

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Statins do not reduce CVD or mortality in elderly without T2DM

2018

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Primary prevention with statins for older adults

Abstract: Patient preference remains the guiding principle while we wait for better evidence

Cited by 5 publications

References 14 publications

Management of high cholesterol levels in older people

Management of high cholesterol levels in older people

Simvastatin profoundly impairs energy metabolism in primary human muscle cells

Statins do not reduce CVD or mortality in elderly without T2DM

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