03 February 2023: Clinical Research
Association Between Pre-Radiofrequency Catheter Ablation Serum Lipid Levels and Recurrence of Atrial Fibrillation in 412 Patients in Beijing, China: A Single-Center StudyZhi-zhao Li12ABCDEFG*, Ting Liu3F, Qiong Huang4F, Xiao-xia Liu2A, Yu-Qing Song1F, Xue-yuan Guo2A, Chang-sheng Ma2A
Med Sci Monit 2023; 29:e938288
BACKGROUND: This study from a single center in Beijing, China, included 412 patients with atrial fibrillation (AF) who underwent radiofrequency catheter ablation. We aimed to determine whether pre-ablation serum lipid levels were related to recurrence of atrial fibrillation (RAF).
MATERIAL AND METHODS: A total of 412 patients with AF who underwent radiofrequency catheter ablation were enrolled in the study. Fasting levels of triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC), were measured at baseline before ablation, and patients were classified according to lipid level quartiles (Q1-Q4). RAF was affirmed via 24-h electrocardiography or 12-lead electrocardiography.
RESULTS: A total of 82 (19.90%) patients experienced RAF. After adjusting for other relevant factors and sex, univariate logistic regression analysis revealed LDL-C (hazard ratio [HR], 1.17; 95% confidence interval [CI], 0.93-1.47) and TC (HR, 1.17; 95% CI, 0.96-1.42) levels were not significantly related to RAF. Multivariate logistic regression analysis revealed that, compared with the highest quartile (Q4), female patients with lower quartiles of TC had higher RAF, especially Q3 (HR, 16.24; 95% CI, 1.14-231.56). LDL-C levels were higher in Q1 than in Q4 but lower in Q2 and Q3 than in Q4 (Q1: HR, 1.34; 95% CI, 0.08-18.89; Q2: HR, 0.09, 95% CI, 0.06-1.52; Q3: HR, 0.02, 95% CI, 0.14-0.57).
CONCLUSIONS: This study showed RAF in almost 20% of treated patients and RAF was significantly related to pre-ablation serum levels of LDL-C and TC in women.
Keywords: Atrial Fibrillation, Catheter Ablation, Lipids, Neoplasm Recurrence, Local
One of independent risk factors for cardiovascular disease is dyslipidemia; however, its relationship with the occurrence of atrial fibrillation (AF) is still controversial. In a recent review , 84 studies reporting on the effects of cardiovascular risk factors on the incidence of AF in 32 independent cohorts were systematically analyzed, and serum cholesterol levels were found to be negatively correlated with the incidence of AF. Previous studies [2–4] have demonstrated a negative correlation between cholesterol and AF, indicating that low cholesterol levels lead to a high risk of AF. Previous prospective cohort studies have shown that low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels are negatively correlated with the incidence of AF [5,6]. In a case-control study, we found that blood lipid levels were lower in patients with AF than in healthy individuals, especially LDL-C and high-density lipoprotein cholesterol (HDL-C) levels, indicating that LDL-C may increase the susceptibility of patients to AF . Risk factors for the occurrence and recurrence of AF may be similar. The technique of radiofrequency catheter ablation has made significant progress in the treatment of AF; however, the high recurrence rate of AF after catheter ablation remains a major concern, and prognostic factors associated with RAF remain unknown . Moreover, whether lipid levels affect RAF after catheter ablation remains unknown. Therefore, this study from a single center in Beijing, China, included 412 patients with AF who underwent catheter ablation and aimed to determine whether pre-ablation serum lipid levels were associated with RAF after catheter ablation.
Material and Methods
All patients provided written informed consent, and the study was approved by the Ethics Committee of Beijing Anzhen Hospital Capital Medical University. In this case-control study, 412 patients with AF who received circumferential pulmonary vein ablation from January 2017 to December 2017 were included. Paroxysmal AF (PAF) was ablated by the circumferential pulmonary vein, and persistent AF (CAF) was ablated by the circumferential pulmonary vein plus the left top line, mitral isthmus line, and tricuspid isthmus line. After ablation, antiarrhythmic drugs were routinely taken for 3 months. According to the diagnostic criteria of the 2020 Atrial Fibrillation Guidelines , clinical AF can be diagnosed via standard 12-lead electrocardiography or single-lead electrocardiography of ≥30 s showing undiscernible repeated P waves and irregular RR intervals (when atrial-ventricular conduction is not impaired). RAF was defined as AF, flutter, and atrial tachycardia events lasting for ≥30 s after 3 months of catheter ablation and confirmed via standard 12-lead electrocardiography or 24-h Holter monitoring. The exclusion criteria were as follows: severe hepatic or renal dysfunction, autoimmune or inflammatory disease, malignancy, New York Heart Association grade III and IV disease, severe mitral stenosis, left atrial thrombosis, hyperthyroid or hypothyroidism, and percutaneous coronary intervention within 6 months before ablation. Clinical, echocardiographic, and laboratory assessments were performed before ablation. The study was performed in accordance with the relevant guidelines and regulations.
Data regarding baseline characteristics were collected at admission and included smoking status, sex, age, alcohol use, AF type, body mass index (BMI), hypertension, diabetes, history of coronary heart disease, and medication use (eg, lipid-lowering drugs [LLDs]). Both persistent and long-term persistent AF were referred to as non-paroxysmal AF.
DETERMINATION OF BLOOD LIPID LEVELS:
Fasting blood samples were collected on the first morning of admission to evaluate several biochemical indicators, including blood lipids, triglyceride (TG), HDL-C, LDL-C, and TC levels, which were determined via enzymatic colorimetric methods (Zhongsheng Company). According to the quartile grouping of lipid levels, quartiles of TG were determined as follows: Q1, <0.91 mmol/L; Q2, 0.91–1.24 mmol/L; Q3, 1.24–1.67 mmol/L; and Q4, >1.67 mmol/L. Quartiles of HDL-C were determined as follows: Q1, <1.03 mmol/L; Q2, 1.03–1.19 mmol/L; Q3, 1.19–1.38 mmol/L; and Q4, >1.38 mmol/L. Quartiles of LDL-C were determined as follows: Q1, <2.07 mmol/L; Q2, 2.07–2.72 mmol/L; Q3, 2.72–3.36 mmol/L; and Q4, >3.36 mmol/L. Quartiles of TC were determined as follows: Q1, <2.07 mmol/L; Q2, 2.07–2.72 mmol/L; Q3, 2.72–3.36 mmol/L; and Q4, >3.36 mmol/L.
Data with normal distribution were expressed as mean±standard deviation and compared via one-way ANOVA. Data with skewed distribution were expressed as the median and inter-quartile range and were compared using the Mann-Whitney U test. Categorical variables were expressed as percentages and compared with the chi-square test.
Patients were divided into quartiles based on lipid levels, and differences in RAF among quartiles were assessed via the chi-square test. A logistic risk model was established to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to examine the relationship between lipid levels and RAF. Two models were used for the correction of logistic regression estimates: model 1 was adjusted for age and sex, whereas model 2 was adjusted for BMI, diabetes, coronary heart disease, PAF, CAF, hypertension, left atrial diameter (LAD), TG levels, HDL-C levels, LDL-C levels, TC levels, C-reactive protein (CRP) levels, ultrasensitive thyroid stimulating hormone (uTSH) levels, fasting plasma glucose (FPG) levels, systolic blood pressure, diastolic blood pressure, and white blood cell (WBC) count. Data of men and women were analyzed separately. A
Detailed information regarding the baseline characteristics of patients in each TC quartile is provided in Table 1. From the lowest to the highest TC quartile, the levels of HDL-C, LDL-C, TG, and uTSH increased gradually. In the second quartile (Q2) of TC, hypertension, CAD, RAF after catheter ablation, and LLD use decreased (P<0.05). Other risk factors did not differ significantly among TC quartiles.
UNIVARIATE LOGISTIC REGRESSION ANALYSIS OF RECURRENCE AND RISK FACTORS OF AF:
Univariate logistic regression analysis (Table 2) revealed that levels of TC (HR, 1.17; 95% CI, 0.964–1.423; P=0.11), LDL-C (HR, 1.17; 95% CI, 0.93–1.47; P=0.19), HDL-C (HR, 1.21; 95% CI, 0.66–2.22; P<0.54), and TG (HR, 1.03; 95% CI, 0.837–1.275; P<0.76) were not associated with RAF. In addition, BMI, sex, age, alcohol use, smoking status, diabetes, CAD, PAF, CAF, LLD use, LAD, uTSH levels, CRP levels, fasting plasma glucose levels, systolic blood pressure, diastolic blood pressure, and WBC counts were found to have no significant correlation with RAF.
QUARTILES OF LIPID LEVELS AND RAF:
Considering lipid levels as a categorical variable (Table 3), univariate logistic regression analysis showed that patients in Q1 and Q3 of TC had an increased risk of RAF compared with patients in the highest quartile (Q4). However, the recurrence rate of AF was not different among LDL-C, HDL-C, and TG quartiles. Analysis based on the multivariate model (model 2) adjusted for BMI, sex, age, alcohol use, smoking status, diabetes, CAD, PAF, CAF, LLD use, LAD, uTSH levels, CRP levels, fasting plasma glucose levels, systolic blood pressure, diastolic blood pressure, and WBC count revealed that the risk of RAF was higher in Q1, Q2, and Q3 than in Q4 of TC (HR, 2.66; 95% CI, 1.0–8.41; P=0.045).
CORRELATION BETWEEN BLOOD LIPID QUARTILES AND RAF BASED ON SEX:
Given that lipid levels were different between men and women (Tables 4, 5), patients were divided based on sex. Multivariate analysis (model 2) revealed that low quartiles of LDL-C and TC were associated with a higher risk of RAF in women (Table 4) but not in men (Table 5).
In addition, no significant correlation was observed between RAF and the levels of HDL-C and TG in male or female patients. The HRs and 95% CIs of different quartiles of lipid levels among women are shown in Table 4. According to the multivariate analysis, HRs and 95% CIs in the quartile with low lipid levels and the highest quartile were as follows: Q1 of TC (HR, 1.36; 95% CI, 0.02–86.16; P=−0.99), Q3 of TC (HR, 16.24; 95% CI, 1.14–231.56; P=0.04), Q1 of LDL-C (HR, 1.34; 95% CI, 0.08–18.89; P=0.83), and Q3 of LDL-C (HR, 0.02; 95% CI, 0.14–0.57; P=0.03). The increase of 1.0 mmol/L in Q1 of LDL-C was associated with a 34% reduction in the risk of RAF. TG and HDL-C levels were not associated with RAF.
CONTINUOUS LIPID LEVELS AND RAF:
Multivariate logistic analysis (Table 6; models 1 and 2) based on the sex of patients showed that elevated levels of TG, HDL-C, LDL-C, and TC were not significantly associated with the reduced risk of RAF among male and female patients.
This study has some limitations. (1) This was a cross-sectional study of patients with RAF from different centers with different operators. (2) A small number of selected participants included elderly patients and postmenopausal women. (3) Patients receiving lipid-lowering treatment and those not receiving the treatment were not separated. (4) Previous studies have shown that low levels of LDL-C and TC are associated with the risk of AF , which is consistent with the results of this study and verifies the study approach. In this study, the lower lipid-lowering treatment group did not have a high RAF, and the effects of lipid-lowering treatment on RAF were minimal. (5) Blood lipid levels should be evaluated at different follow-up time points in the same center and by the same personnel, and patients should be selected at different time points to verify whether statins are suitable for use in AF.
This study showed RAF in almost 20% of treated patients, and RAF was significantly associated with pre-ablation serum levels of LDL-C and TC in women. Identifying risk factors for RAF after catheter ablation allows clinicians to select patients eligible for secondary procedures, increase success rates, and attempt new preventive therapies. Our results suggest that low cholesterol levels increase the risk of RAF, and statins or other LLDs should be carefully used for women undergoing catheter ablation. Prevention of RAF after catheter ablation among patients with low cholesterol levels in clinical practice should be explored further in large-scale studies.
TablesTable 1. Characteristics according to quartiles of total cholesterol level. Table 2. Univariable analysis of recurrence of atrial fibrillation. Table 3. Quartiles of blood lipids and recurrence of atrial fibrillation (total). Table 4. Quartiles of blood lipid levels and recurrence of atrial fibrillation (women). Table 5. Quartiles of blood lipids and recurrence of atrial fibrillation (men). Table 6. Blood lipid profile and risk for recurrence of atrial fibrillation.
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