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Low Lipid Levels and High Variability are Associated With the Risk of New-Onset Atrial Fibrillation.

ABSTRACT: Background While high levels of lipids and lipid variability are established risk factors for atherosclerotic cardiovascular disease, their roles in the development of atrial fibrillation (AF) are unclear, with previous studies suggesting a "cholesterol paradox." Methods and Results A nationwide population-based cohort of 3 660 385 adults (mean age 43.4 years) from the Korean National Health Insurance Service database, with ≥3 annual lipid measurements from 2009 to 2012 and without a history of AF or prescription of lipid-lowering medication before 2012, were identified. Total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides levels were measured, and lipid variability was calculated using variability independent of the mean. The cohort was divided into quartiles by lipid levels and lipid variability and followed up for incident AF. During a median 5.4 years of follow-up, AF was newly diagnosed in 27 581 (0.75%). AF development was inversely associated with high lipid levels (for top versus bottom quartile; total cholesterol, HR 0.78, 95% CI 0.76-0.81; low-density lipoprotein cholesterol, HR 0.81, 95% CI 0.78-0.84; high-density lipoprotein cholesterol, HR 0.94, 95% CI 0.91-0.98; triglycerides, HR 0.88, 95% CI 0.85-0.92). Meanwhile, AF development was associated with high lipid variability (for top versus bottom quartile; total cholesterol, HR 1.09, 95% CI 1.06-1.13; low-density lipoprotein cholesterol, HR 1.12, 95% CI 1.08-1.16; high-density lipoprotein cholesterol, HR 1.08, 95% CI 1.04-1.12; triglycerides, HR 1.05, 95% CI 1.01-1.08). Men showed greater risk reduction with high triglyceride levels and greater risk with high triglyceride variability for incident AF. Conclusions Low cholesterol levels and high cholesterol variability were associated with a higher risk of AF development.

SUBMITTER: Lee HJ

PROVIDER: S-EPMC6912974 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:CONTEXT:Although the heritability of atrial fibrillation (AF) is established, the contribution of familial AF to predicting new-onset AF remains unknown. OBJECTIVE:To determine whether familial occurrence of AF is associated with new-onset AF beyond established risk factors. DESIGN, SETTING, AND PARTICIPANTS:The Framingham Heart Study, a prospective community-based cohort study started in 1948. Original and Offspring Cohort participants were aged at least 30 years, were free of AF at the baseline examination, and had at least 1 parent or sibling enrolled in the study. The 4421 participants in this analysis (mean age, 54 [SD, 13] years; 54% women) were followed up through December 31, 2007. MAIN OUTCOME MEASURES:Incremental predictive value of incorporating different features of familial AF (any familial AF, premature familial AF [onset ?65 years old], number of affected relatives, and youngest age of onset in a relative) into a risk model for new-onset AF. RESULTS:Across 11,971 examinations during the period 1968-2007, 440 participants developed AF. Familial AF occurred among 1185 participants (26.8%) and premature familial AF occurred among 351 participants (7.9%). Atrial fibrillation occurred more frequently among participants with familial AF than without familial AF (unadjusted absolute event rates of 5.8% and 3.1%, respectively). The association was not attenuated by adjustment for AF risk factors (multivariable-adjusted hazard ratio, 1.40; 95% confidence interval [CI], 1.13-1.74) or reported AF-related genetic variants. Among the different features of familial AF examined, premature familial AF was associated with improved discrimination beyond traditional risk factors to the greatest extent (traditional risk factors, C statistic, 0.842 [95% CI, 0.826-0.858]; premature familial AF, C statistic, 0.846 [95% CI, 0.831-0.862]; P = .004). Modest changes in integrated discrimination improvement were observed with premature familial AF (2.1%). Net reclassification improvement (assessed using 8-year risk thresholds of <5%, 5%-10%, and >10%) did not change significantly with premature familial AF (index statistic, 0.011; 95% CI, -0.021 to 0.042; P = .51), although categoryless net reclassification was improved (index statistic, 0.127; 95% CI, 0.064-0.189; P = .009). CONCLUSIONS:In this cohort, familial AF was associated with an increased risk of AF that was not attenuated by adjustment for AF risk factors including genetic variants. Assessment of premature familial AF was associated with a very slight increase in predictive accuracy compared with traditional risk factors.

Project description:IMPORTANCE:A substantial proportion of patients with atrial fibrillation (AF) die of noncardiovascular causes, and recent studies suggest a link between AF and cancer. OBJECTIVE:To evaluate the associations between AF and cancer in a large, long-term prospective cohort study. DESIGN, SETTING, AND PARTICIPANTS:In this cohort study, a total of 34 691 women 45 years or older and free of AF, cardiovascular disease, and cancer at baseline were prospectively followed up between 1993 and 2013, for incident AF and malignant cancer within the Women's Health Study, a randomized clinical trial of aspirin and vitamin E for the prevention of cardiovascular disease and cancer. Cox proportional hazards models using time-updated covariates were constructed to assess the association of new-onset AF with subsequent cancer and to adjust for potential confounders. Data analysis was performed from December 2014 to May 2015. EXPOSURE:New-onset AF. MAIN OUTCOMES AND MEASURES:Incident malignant cancer confirmed by an end point committee. RESULTS:During a median follow-up of 19.1 years of 34 691 study participants (interquartile range [IQR], 17.6-19.7 years), new-onset AF and malignant cancer were confirmed among 1467 (4.2%) and 5130 (14.8%) participants, respectively. Median age at baseline among participants with new-onset AF and new-onset cancer during follow-up was 58 years (IQR, 52-64 years) and 55 years (IQR, 50-61 years), respectively. Atrial fibrillation was a significant risk factor for incident cancer in age-adjusted (hazard ratio [HR], 1.58; 95% CI, 1.34-1.87; P?<?.001) and multivariable-adjusted (HR, 1.48; 95% CI, 1.25-1.75; P?<?.001) models. The relative risk of cancer was highest in the first 3 months after new-onset AF (HR, 3.54; 95% CI, 2.05-6.10; P?<?.001) but remained significant beyond 1 year after new-onset AF (adjusted HR, 1.42; 95% CI, 1.18-1.71; P?<?.001), and a trend toward an increased cancer mortality was observed (adjusted HR, 1.32; 95% CI, 0.98-1.79; P?=?.07). In contrast, among women with new-onset cancer, the relative risk of AF was increased only within the first 3 months (HR, 4.67; 95% CI, 2.85-7.64; P?<?.001) but not thereafter (HR, 1.15; 95% CI, 0.95-1.39; P?=?.15). CONCLUSIONS AND RELEVANCE:In this large, initially healthy cohort, women with new-onset AF had an elevated cancer risk beyond 1 year of AF diagnosis. Shared risk factors and/or common systemic disease processes might underlie this association.

Project description:ImportanceAtrial fibrillation (AF) is the most common cardiac arrhythmia worldwide, with different epidemiological and pathophysiological processes for women vs men and a poorer prognosis for women. Further investigation of sex-specific risk factors associated with AF development in women is warranted.ObjectiveTo investigate the linear and potential nonlinear associations between sex-specific risk factors and the risk of new-onset AF in women.Design, setting, and participantsThis population-based cohort study obtained data from the 2006 to 2010 UK Biobank study, a cohort of more than 500 000 participants aged 40 to 69 years. Participants were women without AF and history of hysterectomy and/or bilateral oophorectomy at baseline. Median follow-up period for AF onset was 11.6 years, and follow-up ended on October 3, 2020.ExposuresSelf-reported, sex-specific risk factors, including age at menarche, history of irregular menstrual cycle, menopause status, age at menopause, years after menopause, age at first live birth, years after last birth, history of spontaneous miscarriages, history of stillbirths, number of live births, and total reproductive years.Main outcomes and measuresThe primary outcome was new-onset AF, which was defined by the use of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code I48.ResultsA total of 235 191 women (mean [SD] age, 55.7 [8.1] years) were included in the present study. During follow-up, 4629 (2.0%) women experienced new-onset AF. In multivariable-adjusted models, history of irregular menstrual cycle was associated with higher AF risk (hazard ratio [HR], 1.34; 95% CI, 1.01-1.79). Both early menarche (age 7-11 years; HR, 1.10 [95% CI, 1.00-1.21]) and late menarche (age 13-18 years; HR, 1.08 [95% CI, 1.00-1.17]) were associated with AF incidence. Early menopause (age 35-44 years; HR, 1.24 [95% CI, 1.10-1.39]) and delayed menopause (age ≥60 years; HR, 1.34 [95% CI, 1.10-1.78]) were associated with higher risk of AF. Compared with women with 1 to 2 live births, those with 0 live births (HR, 1.13; 95% CI, 1.04-1.24) or 7 or more live births (HR, 1.67; 95% CI, 1.03-2.70) both had significantly higher AF risk.Conclusions and relevanceResults of this study suggest that irregular menstrual cycles, nulliparity, and multiparity were associated with higher risk of new-onset AF among women. The results highlight the importance of taking into account the reproductive history of women in devising screening strategies for AF prevention.

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Low Lipid Levels and High Variability are Associated With the Risk of New-Onset Atrial Fibrillation.

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