Low‐Dose Statin Therapy Improves Endothelial Function in Type 2 Diabetic Patients With Normal Serum Total Cholesterol: A Randomized Placebo‐Controlled Study

Adel, Amr; Abdel-Salam, Zainab; Nammas, Wail

doi:10.1111/j.1751-7176.2010.00367.x

Cited by 14 publications

(10 citation statements)

References 21 publications

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“…The decreased mortality rate from cardiovascular diseases following statin consumption was attributed to both the lipid-lowering effect and enhancement of vascular endothelial function [ 18 – 20 ]. The latter statin-effect has also been observed in other patient populations, including diabetics [ 21 , 22 ] and women with polycystic ovary syndrome [ 23 ]. Various mechanisms have been reported for the statin-mediated improvement of endothelial function and include reducing remnant lipoproteins [ 24 ], modulating the high mobility group box 1/toll-like receptor 4(HMGB1/TLR4) pathway [ 25 ], inhibiting miR-133a expression [ 26 ], inducing nitric oxide release [ 27 ], affecting Kruppel-like factor 2 signaling [ 28 ], and decreasing the level of acute-phase proteins (like C-reactive protein) [ 29 ]; of note, this last mechanism is also involved in the anti-inflammatory effects of statins [ 29 , 30 ].…”

Section: Introductionmentioning

confidence: 76%

Statins in patients with COVID-19: a retrospective cohort study in Iranian COVID-19 patients

et al. 2021

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Background The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has profoundly affected the lives of millions of people. To date, there is no approved vaccine or specific drug to prevent or treat COVID-19, while the infection is globally spreading at an alarming rate. Because the development of effective vaccines or novel drugs could take several months (if not years), repurposing existing drugs is considered a more efficient strategy that could save lives now. Statins constitute a class of lipid-lowering drugs with proven safety profiles and various known beneficial pleiotropic effects. Our previous investigations showed that statins have antiviral effects and are involved in the process of wound healing in the lung. This triggered us to evaluate if statin use reduces mortality in COVID-19 patients. Results After initial recruitment of 459 patients with COVID-19 (Shiraz province, Iran) and careful consideration of the exclusion criteria, a total of 150 patients, of which 75 received statins, were included in our retrospective study. Cox proportional-hazards regression models were used to estimate the association between statin use and rate of death. After propensity score matching, we found that statin use appeared to be associated with a lower risk of morbidity [HR = 0.85, 95% CI = (0.02, 3.93), P = 0.762] and lower risk of death [(HR = 0.76; 95% CI = (0.16, 3.72), P = 0.735)]; however, these associations did not reach statistical significance. Furthermore, statin use reduced the chance of being subjected to mechanical ventilation [OR = 0.96, 95% CI = (0.61–2.99), P = 0.942] and patients on statins showed a more normal computed tomography (CT) scan result [OR = 0.41, 95% CI = (0.07–2.33), P = 0.312]. Conclusions Although we could not demonstrate a significant association between statin use and a reduction in mortality in patients with COVID19, we do feel that our results are promising and of clinical relevance and warrant the need for prospective randomized controlled trials and extensive retrospective studies to further evaluate and validate the potential beneficial effects of statin treatment on clinical symptoms and mortality rates associated with COVID-19.

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Section: Introductionmentioning

confidence: 76%

Statins in patients with COVID-19: a retrospective cohort study in Iranian COVID-19 patients

et al. 2021

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“…Improvement in endothelial function occurred within days of treatment, prior to any plasma lipid changes and was correlated with a reduction in oxidative stress, inflammation and endothelial cell activation [109][110][111][112]. In normocholesterolemic T2D patients without evidence of CAD, 4 weeks of low dose atrovastatin significantly improved brachial artery FMD compared with placebo [113]. In a placebocontrolled study in T2D patients, atorvastatin was associated with a reduction in vascular cell adhesion molecules (VCAM-I) and E-selectin, suggesting an improvement in endothelial function that was independent of the lipid-regulating effects of atorvastatin [114].…”

Section: Lipid-regulating Therapymentioning

confidence: 95%

“…The evidence from studies examining the effects of statins on ED in T2D has been inconsistent and contradictory (Table 3) [109][110][111][112][113][114][115][116][117][118][119][120][121][122][123]. It is possible that in T2D, treatment with a single therapeutic agent may not adequately improve ED and that combination therapy is required.…”

Section: Combination Therapiesmentioning

confidence: 99%

Endothelial Dysfunction in Diabetes: Pathogenesis, Significance, and Treatment

2013

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■ AbstractType 2 diabetes (T2D) markedly increases the risk of cardiovascular disease. Endothelial dysfunction (ED), an early indicator of diabetic vascular disease, is common in T2D and independently predicts cardiovascular risk. Although the precise pathogenic mechanisms for ED in T2D remain unclear, at inception they probably involve uncoupling of both endothelial nitric oxide synthase activity and mitochondrial oxidative phosphorylation, as well as the activation of vascular nicotinamide adenine dinucleotide phosphate oxidase. The major contributing factors include dyslipoproteinemia, oxidative stress, and inflammation. Therapeutic interventions are designed to target these pathophysiological factors that underlie ED. Therapeutic interventions, including lifestyle changes, antiglycemic agents and lipid-regulating therapies, aim to correct hyperglycemia and atherogenic dyslipidemia and to improve ED. However, high residual cardiovascular risk is seen in both research and clinical practice settings. Well-designed studies of endothelial function in appropriately selected volunteers afford a good opportunity to test new therapeutic interventions, paving the way for clinical trials and utilization in the care of the diabetic patient. However, based on the results from a recent clinical trial, niacin should not be added to a statin in individuals with low high-density lipoprotein cholesterol and very well controlled low-density lipoprotein cholesterol.

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“…The decreased mortality rate from cardiovascular diseases following statin consumption was attributed to both the lipid-lowering effect and enhancement of the vascular endothelial function [17][18][19]. The latter statin-effect has also been observed in other patient populations, including diabetics [20,21] and women with polycystic ovary syndrome [22]. Various mechanisms have been reported for the statinmediated improvement of endothelial function, e.g.…”

Section: Introductionmentioning

confidence: 99%

Statins in Patients with COVID-19: A Retrospective Cohort Study in Iranian COVID-19 Patients

Peymani

Dehesh

Aligolighasemabadi

et al. 2020

Preprint

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Background: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has profoundly affected the lives of millions of people. To date, there is no approved vaccine or specific drug to prevent or treat COVID-19, while the infection is spreading at an alarming rate globally. Because the development of effective vaccines or novel drugs could take several months (if not years), repurposing existing drugs is considered a more efficient strategy that could save lives now. Statins constitute a class of lipid-lowering drugs with proven safety profiles and many known beneficial pleiotropic effects. Our previous investigations showed that statins have antiviral effects and are involved in the process of wound healing in the lung. This triggered us to evaluate if statin use reduces mortality in COVID-19 patients. Results: After initial recruitment of 459 patients with COVID-19 (Shiraz province, Iran) and careful consideration of the exclusion criteria, a total of 150 patients, of which 75 received statins, were included in our retrospective study. Cox proportional-hazards regression models were used to estimate the association between statin use and rate of death. After propensity score matching, we found that statin use appeared to be associated with a lower risk of morbidity [HR=0.85, 95% CI=(0.02, 3.93), P=0.762] and lower risk of death [(HR= 0.76; 95% CI=(0.16, 3.72), P=0.735)]; however, these associations did not reach statistical significance. Furthermore, statin use reduced the chance of being subjected to mechanical ventilation [OR=0.96, 95% CI=(0.61–2.99), P=0.942] and patients on statins had a more normal computed tomography (CT) scan result [OR=0.41, 95% CI= (0.07–2.33), P=0.312]. Conclusions: Although we could not demonstrate a significant association between statin use and a reduction in mortality in patients with COVID19 , we do feel that our results are promising and of clinical relevance and warrant the need for prospective randomized controlled trials and extensive retrospective studies to validate the potential beneficial effects of statin treatment on clinical symptoms and mortality rates associated with COVID-19.

show abstract

Low‐Dose Statin Therapy Improves Endothelial Function in Type 2 Diabetic Patients With Normal Serum Total Cholesterol: A Randomized Placebo‐Controlled Study

Cited by 14 publications

References 21 publications

Statins in patients with COVID-19: a retrospective cohort study in Iranian COVID-19 patients

Statins in patients with COVID-19: a retrospective cohort study in Iranian COVID-19 patients

Endothelial Dysfunction in Diabetes: Pathogenesis, Significance, and Treatment

Statins in Patients with COVID-19: A Retrospective Cohort Study in Iranian COVID-19 Patients

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