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Lack of Atorvastatin Protective Effect Against Atrial Fibrillation in CETP TaqIB2B2 Genotype
Francesca Galati1, Antonio Galati2, Serafina Massari1
1Department of Biological and Environmental Sciences and Technologies - University of Salento, Lecce, Italy.
Insights
Genetic variations in CETP TaqIB polymorphism may increase atrial fibrillation risk in patients taking statins. Specifically, the B2B2 genotype appears linked to higher AF occurrence, suggesting statins might counteract their own benefits in these individuals.
Area of Science:
- Cardiovascular Genetics
- Pharmacogenomics
- Lipid Metabolism
Background:
- Statins are used to reduce cardiovascular risk, but their effect on atrial fibrillation (AF) varies.
- Cholesteryl ester transfer protein (CETP) expression influences statin response.
- CETP TaqIB polymorphism is a potential genetic factor affecting AF risk.
Purpose of the Study:
- To investigate if CETP TaqIB polymorphism influences atrial fibrillation occurrence in patients treated with atorvastatin.
- To explore the interaction between statin therapy, CETP genotype, and AF development.
Main Methods:
- Case-control study involving dyslipidemic patients on atorvastatin and normolipidemic controls.
- Genotyping of CETP TaqIB polymorphism using RFLP-PCR.
- Follow-up for AF episodes over a mean period of 71 months.
Main Results:
- Atorvastatin treatment was associated with a statistically significant reduction in AF episodes compared to the control group (32% vs 44%, p=0.0208).
- In patients treated with atorvastatin, the B2B2 genotype was significantly more frequent in those who developed AF (p=0.0001).
- Subjects with the B2B2 genotype showed increased susceptibility to AF (RR 2.74, p<0.025).
Conclusions:
- The CETP TaqIB B2B2 genotype may predispose individuals to atrial fibrillation, particularly when treated with statins.
- Statins might have an adverse effect on AF risk in individuals with genetically determined low CETP levels.
- Reduced CETP activity by statins in genetically susceptible individuals could potentially counteract the cardioprotective effects of statins regarding AF.
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.
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