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Lack of Atorvastatin Protective Effect Against Atrial Fibrillation in CETP TaqIB2B2 Genotype.

ABSTRACT: There has been some evidence for a role of statins in reducing the risk of atrial fibrillation, but the response to statin treatment varies considerably due to environmental and genetic factors. One of these is related to CETP expression. So we assessed whether CETP TaqIB polymorphism influences atrial fibrillation occurrence after treatment with statins. 200 unrelated dyslipidemic Caucasian patients (146 men and 54 women; mean age 75±8) from Salento (Southern Italy), assigned to atorvastatin treatment, and 158 normolipidemic subjects (119 men and 39 women; mean age 75±11), selected from the same ward, were enrolled. All patients were followed at six-month intervals. CETP TaqIB polymorphism was genotyped by RFLP-PCR. During a mean follow-up time of 71±6 months, 64 patients (32%) of the group treated with atorvastatin and 70 subjects (44%) of the group without atorvastatin experienced at least one episode of AF, with a statistically significant difference (p = 0,0208) between the two groups. No significant differences were observed between the two groups with regard to demographic and echocardiographic data, to clinical history and pharmacological treatment. While in patients not assuming atorvastatin there was no significant difference (p = 1) between TaqIB genotype and atrial fibrillation occurence, in subjects treated with atorvastatin B2B2 genotype was more frequent in patients with atrial fibrillation (p = 0,0001). According to these data the subjects with the B2B2 genotype seem to be more susceptible to atrial fibrillation development (RR 2,74; IC 95% 1,92-3,90; p<0.025). Our data seem to provide a further evidence for the hypothesis that statins may have adverse effect in subjects with genetically low CETP levels. Because statins reduce CETP activity up to 30%, we hypothesize that such CETP activity reduction by statins, in patients with low CETP levels induced by polymorphism, may counteract the beneficial effect of statins on atrial fibrillation.

SUBMITTER: Galati F

PROVIDER: S-EPMC5135112 | biostudies-literature | 2015 Jun-Jul

REPOSITORIES: biostudies-literature

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Lack of Atorvastatin Protective Effect Against Atrial Fibrillation in CETP TaqIB2B2 Genotype.

Galati Francesca F Galati Antonio A Massari Serafina S

Journal of atrial fibrillation 20150630 1

There has been some evidence for a role of statins in reducing the risk of atrial fibrillation, but the response to statin treatment varies considerably due to environmental and genetic factors. One of these is related to CETP expression. So we assessed whether CETP TaqIB polymorphism influences atrial fibrillation occurrence after treatment with statins. 200 unrelated dyslipidemic Caucasian patients (146 men and 54 women; mean age 75±8) from Salento (Southern Italy), assigned to atorvastatin tr ...[more]

PMID: 27957173

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Project description:The mouse is a useful preclinical species for evaluating disease etiology due to the availability of a wide variety of genetically modified strains and the ability to perform disease-modifying manipulations. In order to establish an atrial filtration (AF) model in our laboratory, we profiled several commonly used murine AF models. We initially evaluated a pharmacological model of acute carbachol (CCh) treatment plus atrial burst pacing in C57BL/6 mice. In an effort to observe micro-reentrant circuits indicative of authentic AF, we employed optical mapping imaging in isolated mouse hearts. While CCh reduced atrial refractoriness and increased atrial tachyarrhythmia vulnerability, the left atrial (LA) excitation patterns were rather regular without reentrant circuits or wavelets. Therefore, the atrial tachyarrhythmia resembled high frequency atrial flutter, not typical AF per se. We next examined both a chronic angiotensin II (Ang II) infusion model and the surgical model of transverse aortic constriction (TAC), which have both been reported to induce atrial and ventricular structural changes that serve as a substrates for micro-reentrant AF. Although we observed some extent of atrial remodeling such as fibrosis or enlarged LA diameter, burst pacing-induced atrial tachyarrhythmia vulnerability did not differ from control mice in either model. This again suggested that an AF-like pathophysiology is difficult to demonstrate in the mouse. To continue searching for a valid murine AF model, we studied mice with a cardiac-specific deficiency (KO) in liver kinase B1 (Cardiac-LKB1), which has been reported to exhibit spontaneous AF. Indeed, the electrocardiograms (ECG) of conscious Cardiac-LKB1 KO mice exhibited no P waves and had irregular RR intervals, which are characteristics of AF. Histological evaluation of Cardiac-LKB1 KO mice revealed dilated and fibrotic atria, again consistent with AF. However, atrial electrograms and optical mapping revealed that electrical activity was limited to the sino-atrial node area with no electrical conduction into the atrial myocardium beyond. Thus, Cardiac-LKB1 KO mice have severe atrial myopathy or atrial standstill, but not AF. In summary, the atrial tachyarrhythmias we observed in the four murine models were distinct from typical human AF, which often exhibits micro- or macro-reentrant atrial circuits. Our results suggest that the four murine AF models we examined may not reflect human AF well, and raise a cautionary note for use of those murine models to study AF.

Dataset Information

Lack of Atorvastatin Protective Effect Against Atrial Fibrillation in CETP TaqIB2B2 Genotype.

Publications

Lack of Atorvastatin Protective Effect Against Atrial Fibrillation in CETP TaqIB2B2 Genotype.

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