Obesity and statins are both independent predictors of enhanced coronary arteriolar dilation in patients undergoing heart surgery

Cassuto, James; Fehér, Attila; Lan, Ling; Patel, Vijay; Kamath, Vinayak; Anthony, Daniel C.; Bagi, Zsolt

doi:10.1186/1749-8090-8-117

Cited by 6 publications

(6 citation statements)

References 27 publications

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“…Obesity is considered one of the most potent risk factors for many cardiovascular diseases, and is growing in prevalence in older adults at an alarming rate. 8 Our earlier studies showed that in mice and rats with HFD-induced obesity 32, 33 and also in obese patients 34, 35 coronary arteriole dilator function is surprisingly preserved, in spite of significant adiposity and weight gain and elevated glucose and serum lipid levels. In the present study we also found that younger obese patients as well as younger HFD-fed obese mice have maintained endothelium-dependent coronary arteriole dilations.…”

Section: Discussionmentioning

confidence: 99%

Role of Adipose Tissue Endothelial ADAM17 in Age-Related Coronary Microvascular Dysfunction

Dou

Fehér

Davila

et al. 2017

ATVB

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Objective A disintegrin and metalloproteinase ADAM17 (TNF-α converting enzyme) regulates soluble TNF levels. We tested the hypothesis that aging-induced activation in adipose tissue (AT)-expressed ADAM17 contributes to the development of remote coronary microvascular dysfunction (CMD) in obesity. Approach and Results Coronary arterioles (CA,~90 μm) from right atrial appendages and mediastinal AT were examined in patients (age:69±11yrs.,BMI:30.2±5.6) who underwent open-heart surgery. CA and AT were also studied in 6-month and 24-month lean and obese mice fed a normal or high-fat diet (HFD). We found that obesity elicited impaired endothelium-dependent CA dilations only in older patients and in aged HFD mice. Transplantation of AT from aged obese, but not from young or aged mice increased serum cytokine levels, including TNF, and impaired CA dilation in the young recipient mice. In patients and mice obesity was accompanied by age-related activation of ADAM17, which was attributed to vascular endothelium-expressed ADAM17. Excess, ADAM17-shed TNF from AT arteries in older obese patients was sufficient to impair CA dilation in a bioassay in which the AT artery was serially connected to a CA. Moreover, we found that the increased activity of endothelial ADAM17 is mediated by a diminished inhibitory interaction with caveolin-1, owing to age-related decline in caveolin-1 expression in obese patients and mice or to genetic deletion of caveolin-1. Conclusions The present study indicates that aging and obesity cooperatively reduce Cav1 expression, increase vascular endothelial ADAM17 activity and soluble TNF release in AT, which may contribute to the development of remote CMD in older obese patients.

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Section: Discussionmentioning

confidence: 99%

Role of Adipose Tissue Endothelial ADAM17 in Age-Related Coronary Microvascular Dysfunction

Dou

Fehér

Davila

et al. 2017

ATVB

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“…had reported in their study that there is an independent association with a heightened possibility of evolution of diabetes, between obesity and statin therapy. [ 13 ] The mean waist circumference of the study participants in the present study was 95.97 ± 6.30 among males and 87.48 ± 4.64 among females. In the study conducted by Thomson et al ., 86.41 ± 9.13 cm was the mean waist circumference.…”

Section: Discussionmentioning

confidence: 59%

Evaluation of glycemic status among hypercholesterolemic patients on atorvastatin in a tertiary care hospital – A retrospective study

Ramarao

Ramya

Karthick

2022

Indian Journal of Pharmacology

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INTRODUCTION: Statins are effective in reducing low-density lipoprotein cholesterol and are favorable in primary and secondary prevention of cardiovascular disease. Recent large trials have linked the use of statins and increased incidence of new-onset diabetes mellitus, the possibility of worsening of glucose level in individuals with diabetes following statin therapy, and this possibility is increased with the use of atorvastatin. This study was undertaken to analyze the possibility of the diabetogenic potential of atorvastatin among hypercholesterolemic patients. MATERIALS AND METHODS: This retrospective cohort study was conducted in the cardiology department from July 2019 to December 2019. Patients on atorvastatin for more than 6 months with normoglycemia on commencement of therapy were included. The occurrence of prediabetes or new-onset diabetes mellitus after atorvastatin therapy is the outcome of the study. Adverse drug effects to atorvastatin were also recorded and WHO-UMC causality assessment was performed. Descriptive statistics were performed for baseline and demographic characteristics. RESULTS: Sixty study participants were included in the study. Eighteen (30%) study participants developed prediabetes with an HbA1c value of 5.97 ± 0.22 and 17 (28%) of participants developed new-onset diabetes mellitus with an HbA1c value of 7.24 ± 0.50. Atorvastatin at dose of 40 mg was found to be the most frequently prescribed dose. CONCLUSION: Atorvastatin has a dose-dependent risk of developing new-onset diabetes mellitus. Hence, the following statin therapy glycemic status should be periodically monitored especially in patients with a large dose of atorvastatin and also in patients with higher risk factors for diabetes.

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“…This is in accordance with the study conducted by Cassuto et al ., who reported that obesity and statin therapy are independently associated with an enhanced risk for the development of diabetes. [22] However, in WOSCOPS, LIPID, HPS, and ASCOTT trials, larger proportions of patients were in the overweight category. This could be the probable reason for higher proportions of diabetes in these trials in comparison to the present study.…”

Section: Discussionmentioning

confidence: 99%

Analysis of glycemic status in diabetes-naïve patients on statins: A hospital-based cross-sectional study

et al. 2018

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INTRODUCTION:Randomized controlled trials, observational studies, and meta-analysis suggest risk of hyperglycemia in patients on statins, and this association is being viewed with renewed interest globally. The present study has tried to explore the possible diabetogenic effect of statins, the mechanism of this effect, and various comorbidities associated with this causation.MATERIALS AND METHODS:This cross-sectional study was carried out at the Department of Cardiology from October 2015 to March 2017. Patients on statins for at least 1 year and normoglycemic at the time of statin initiation were recruited in the study. The outcome of the present study was development of new-onset diabetes mellitus (NODM). Blood glucose levels and insulin levels were estimated. Other adverse reactions of statins and associated comorbidities in the patients were recorded. Descriptive statistics were used to analyze adverse drug reactions.RESULTS:A total of 104 patients met the inclusion criteria, of which eight patients (7.7%) developed NODM and 4 (3.8%) developed prediabetes. Atorvastatin 40 mg was most commonly prescribed statin. About 25% of patients taking atorvastatin 80 mg developed diabetesCONCLUSION:Statins have a mild-to-moderate risk of developing NODM. The dose of statins is an important factor that increases the risk of diabetes in statin users

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Obesity and statins are both independent predictors of enhanced coronary arteriolar dilation in patients undergoing heart surgery

Cited by 6 publications

References 27 publications

Role of Adipose Tissue Endothelial ADAM17 in Age-Related Coronary Microvascular Dysfunction

Role of Adipose Tissue Endothelial ADAM17 in Age-Related Coronary Microvascular Dysfunction

Evaluation of glycemic status among hypercholesterolemic patients on atorvastatin in a tertiary care hospital – A retrospective study

Analysis of glycemic status in diabetes-naïve patients on statins: A hospital-based cross-sectional study

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