Levothyroxine treatment and incident dementia in adults with atrial fibrillation.
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ABSTRACT:
SUBMITTER: Wandell P
PROVIDER: S-EPMC6872912 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND AND OBJECTIVE:The possible adverse or positive effects of levothyroxine treatment among patients with atrial fibrillation have been debated. Atrial fibrillation, levothyroxine treatment, and dementia are common among older adults, yet little is known about the effects of levothyroxine on the development of dementia. METHODS:The study population included all adults (n?=?12,057) aged???45 years with a diagnosis of atrial fibrillation at 75 primary care centers in Sweden during 2001-2007 without an earlier recorded dementia diagnosis. Patients with a diagnosis of hypothyroidism and levothyroxine prescription (n?=?756; 180 men and 576 women), or with a prescription without this diagnosis (n?=?415, 100 men and 315 women), were compared to patients without a diagnosis and prescription (n?=?10,886). Cox regression was performed, with hazard ratios and 95% confidence intervals, with outcome defined as dementia of all causes until 31 December, 2010. RESULTS:During a mean 5.7 years (standard deviation 2.4 years) of follow-up, a total of 749 patients with atrial fibrillation (6.2%) were diagnosed with dementia. Women with hypothyroidism and a levothyroxine prescription showed lower hazard ratios (0.61; 0.41-0.90) in adjusted Cox regression models (age, socioeconomic factors, co-morbidity, and warfarin treatment). Levothyroxine prescription without hypothyroidism was non-significant. CONCLUSIONS:We found that women with atrial fibrillation with levothyroxine treatment and hypothyroidism have a lower risk of incident dementia than women with atrial fibrillation without levothyroxine treatment and no hypothyroidism. The results should be confirmed in larger studies.
| S-EPMC6394624 | biostudies-literature
Project description:Levothyroxine has been suggested to be cardiotoxic, but previous studies on the risk of cardiovascular events associated with levothyroxine treatment have been inconclusive. We aimed to study the association between levothyroxine treatment and all-cause mortality as well as cardiovascular events. Study population included all adults (n?=?12,283)???45 years diagnosed with atrial fibrillation (AF) at 75 primary care centers in Sweden in 2001 to 2007, with (n?=?1,189; 283 men and 906 women) or without (n?=?11,094) levothyroxine treatment. Outcome was defined as all-cause mortality and cardiovascular events, that is, myocardial infarction, ischemic stroke, and congestive heart failure until December 31, 2010. During a mean 5.8 years (standard deviation 2.4 years) of follow-up, a total of 3,954 patients died (32.2%), among whom 92 men (32.5%) and 266 women (29.4%) were treated with levothyroxine. In fully adjusted Cox regression models (age, co-morbidity, socioeconomic factors, and warfarin treatment), a significant association between levothyroxine treatment and lower mortality was found among women (hazard ratio 0.78, 95% confidence interval 0.68 to 0.91), but not among men (hazard ratio 0.87, 95% confidence interval 0.69 to 1.10). In the secondary analysis, levothyroxine treatment was not associated with the risk of myocardial infarction, ischemic stroke, or congestive heart failure (p?>?0.05). In conclusion, in a large representative cohort, we found that levothyroxine treatment decreased the mortality risk in women with AF, which suggests that such treatment could be of benefit in this setting.
| S-EPMC5694377 | biostudies-literature
Project description:ObjectiveThe aim of this study was to investigate the association between oral anticoagulant type (direct oral anticoagulants (DOACs) vs vitamin K antagonists (VKAs)) and incident dementia or mild cognitive impairment (MCI) among patients with newly diagnosed atrial fibrillation (AF).MethodsUsing linked electronic health record (EHR) data from the Clinical Practice Research Datalink in the UK, we conducted a historical cohort study among first-time oral anticoagulant users with incident non-valvular AF diagnosed from 2012 to 2018. We compared the incidence of (1) clinically coded dementia and (2) MCI between patients prescribed VKAs and DOACs using Cox proportional hazards regression models, with age as the underlying timescale, accounting for calendar time and time on treatment, sociodemographic and lifestyle factors, clinical comorbidities and medications.ResultsOf 39 200 first-time oral anticoagulant users (44.6% female, median age 76 years, IQR 68-83), 20 687 (53%) were prescribed a VKA and 18 513 (47%) a DOAC at baseline. Overall, 1258 patients (3.2%) had GP-recorded incident dementia, incidence rate 16.5 per 1000 person-years. DOAC treatment for AF was associated with a 16% reduction in dementia diagnosis compared with VKA treatment in the whole cohort (adjusted HR 0.84, 95% CI: 0.73 to 0.98) and with a 26% reduction in incident MCI (adjusted HR 0.74, 95% CI: 0.65 to 0.84). Findings were similar across various sensitivity analyses.ConclusionsIncident EHR-recorded dementia and MCI were less common among patients prescribed DOACs for new AF compared with those prescribed VKAs.
| S-EPMC8600601 | biostudies-literature
Project description:Background Atrial fibrillation (AF) is the most common, clinically relevant arrhythmia in adults and associated with ischemic stroke and premature death. However, data are conflicting on whether AF is independently associated with risk of dementia, particularly in diverse populations. Methods and Results We identified all adults from 2 large integrated health care delivery systems between 2010 and 2017 and performed a 1:1 match of incident AF: no AF by age at index date, sex, estimated glomerular filtration rate category, and study site. Subsequent dementia was identified through previously validated diagnosis codes. Fine-Gray subdistribution hazard models were used to examine the association of incident AF (versus no AF) with risk of incident dementia, adjusting for sociodemographics and comorbidity and accounting for competing risk of death. Subgroup analyses by age, sex, race, ethnicity, and chronic kidney disease status were also performed. Among 196 968 matched adults, mean (SD) age was 73.6 (11.3) years, with 44.8% women, and 72.3% White. Incidence rates (per 100 person-years) for dementia over a median follow-up of 3.3 (interquartile range, 1.7-5.4) years were 2.79 (95% CI, 2.72-2.85) and 2.04 (95% CI, 1.99-2.08) per 100 person-years in persons with versus without incident AF, respectively. In adjusted models, incident AF was associated with a significantly greater risk of diagnosed dementia (subdistribution hazard ratio [sHR], 1.13 [95% CI, 1.09-1.16]). With additional adjustment for interim stroke events, the association of incident AF with dementia remained statistically significant (sHR, 1.10 [95% CI, 1.07-1.15]). Associations were stronger for age <65 (sHR, 1.65 [95% CI, 1.29-2.12]) versus ≥65 (sHR, 1.07 [95% CI, 1.03-1.10]) years (interaction P<0.001); and those without (sHR, 1.20 [95% CI, 1.14-1.26]) versus with chronic kidney disease (sHR, 1.06 [95% CI, 1.01-1.11]; interaction P<0.001). No meaningful differences were seen by sex, race, or ethnicity. Conclusions In a large, diverse community-based cohort, incident AF was associated with a modestly increased risk of dementia that was more prominent in younger patients and those without chronic kidney disease but did not substantially vary across sex, race, or ethnicity. Further studies should delineate mechanisms underpinning these findings, which may inform use of AF therapies.
| S-EPMC10111519 | biostudies-literature
Project description:OBJECTIVE:To study the association between time in therapeutic range (TTR) during warfarin therapy and risk of dementia in a population-based cohort of incident atrial fibrillation (AF). PATIENTS AND METHODS:We conducted an observational population-based study of 2800 nondemented patients with incident AF from January 1, 2000, through December 31, 2010. The association of incident dementia with warfarin therapy and TTR was examined using Cox proportional hazards regression models. RESULTS:Mean patient age was 71.2 years; 53% were men (n=1495), and warfarin was prescribed to 50.5% (n=1414) within 90 days of AF diagnosis. Incident dementia diagnosis occurred in 357 patients (12.8%) over a mean ± SD follow-up of 5.0±3.7 years. After adjusting for confounders, warfarin therapy was associated with a reduced incidence of dementia (hazard ratio [HR], 0.80; 95% CI, 0.64-0.99). However, only those in the 2 highest quartiles of TTR were associated with lower risk of dementia. A 10% increase in TTR with a 10% reduction in time spent in the subtherapeutic (HR, 0.71; 95% CI, 0.64-0.79) and supratherapeutic (HR, 0.67; 95% CI, 0.57-0.79) ranges were associated with decreased risk of dementia. CONCLUSION:In the community, warfarin therapy for AF is associated with a 20% reduction in risk of dementia. Increasing TTR on warfarin is associated with reduced risk of dementia. The risk of dementia was reduced with a reduction in time spent in subtherapeutic and supratherapeutic international normalized ratio range. Effective anticoagulation may prevent cognitive impairment in patients with AF.
| S-EPMC5814135 | biostudies-literature
Project description:Atrial fibrillation (AF) is likely secondary to multiple different pathophysiological mechanisms that are increasingly but incompletely understood. Motivated by the hypothesis that 3 previously described electrocardiographic predictors of AF identify distinct AF mechanisms, we sought to determine if these electrocardiographic findings independently predict incident disease. Among Cardiovascular Health Study participants without prevalent AF, we determined whether left anterior fascicular block (LAFB), a prolonged QTC, and atrial premature complexes (APCs) each predicted AF after adjusting for each other. We then calculated the attributable risk in the exposed for each electrocardiographic marker. LAFB and QTC intervals were assessed on baseline 12-lead electrocardiogram (n = 4,696). APC count was determined using 24-hour Holter recordings obtained in a random subsample (n = 1,234). After adjusting for potential confounders and each electrocardiographic marker, LAFB (hazard ratio [HR] 2.1, 95% confidence interval [CI] 1.1 to 3.9, p = 0.023), a prolonged QTC (HR 2.5, 95% CI 1.4 to 4.3, p = 0.002), and every doubling of APC count (HR 1.2, 95% CI 1.1 to 1.3, p <0.001) each remained independently predictive of incident AF. The attributable risk of AF in the exposed was 35% (95% CI 13% to 52%) for LAFB, 25% (95% CI 0.6% to 44%) for a prolonged QTC, and 34% (95% CI 26% to 42%) for APCs. In conclusion, in a community-based cohort, 3 previously established electrocardiogram-derived AF predictors were each independently associated with incident AF, suggesting that they may represent distinct mechanisms underlying the disease.
| S-EPMC5503745 | biostudies-literature
Project description:It is well-known that atrial fibrillation carries an increased risk of stroke and dementia. The connecting pathogenic common mechanism is the thromboembolic state provided by atrial fibrillation, which is responsible for the acute cerebral events, as well as more saddle anatomic lesions, which accumulating over time, could lead to a progressive cognitive decline. It is plausible, instinctively, that oral anticoagulation could decrease this risk, although the possibility of micro-haemorrhages, which cannot be ignored, could make anticoagulation in this contest even dangerous. In this regard, whether there are firm, well established, evidences documenting a significant reduction in stroke occurrence with anticoagulant treatment in atrial fibrillation, the same level of evidences are not supporting the treatment in preventing dementia. Bringing some more clarity to this issue could have some considerable advantages, also in term of healthcare cost containment, considering the high prevalence of atrial fibrillation and dementia in the elderly.
| S-EPMC7270894 | biostudies-literature
Project description:BACKGROUND:Patients with dementia might have higher risk for hemorrhagic complications with anticoagulant therapy prescribed for atrial fibrillation (AF). OBJECTIVE:This study assesses the risks and benefits of warfarin, antiplatelets, and no treatment in patients with dementia and AF. METHODS:Of 49,792 patients registered in the Swedish Dementia Registry 2007-2014, 8,096 (16%) had a previous diagnosis of AF. Cox proportional hazards models were used to calculate the risk for ischemic stroke (IS), nontraumatic intracranial hemorrhage, any-cause hemorrhage, and death. RESULTS:Out of the 8,096 dementia patients with AF, 2,143 (26%) received warfarin treatment, 2,975 (37%) antiplatelet treatment, and 2,978 (37%) had no antithrombotic treatment at the time of dementia diagnosis. Patients on warfarin had fewer IS than those without treatment (5.2% versus 8.7%; p?<?0.001) with no differences compared to antiplatelets. In adjusted analyses, warfarin was associated with a lower risk for IS (HR 0.76, CI 0.59-0.98), while antiplatelets were associated with increased risk (HR 1.25, CI 1.01-1.54) compared to no treatment. For any-cause hemorrhage, there was a higher risk with warfarin (HR 1.28, CI 1.03-1.59) compared to antiplatelets. Warfarin and antiplatelets were associated with a lower risk for death compared to no treatment. CONCLUSIONS:Warfarin treatment in Swedish patients with dementia is associated with lower risk of IS and mortality, and a small increase in any-cause hemorrhage. This study supports the use of warfarin in appropriate cases in patients with dementia. The low percentage of patients on warfarin treatment indicates that further gains in stroke prevention are possible.
| S-EPMC5798527 | biostudies-literature
Project description:Atrial fibrillation (AF) is associated with short-term mortality after ST-elevation myocardial infarction (STEMI), but there is limited data on the temporal association between AF and mortality after STEMI. A total of 830 patients were included (age: 62 ± 12 years, 76 % male). Patients with new-onset AF < 30 days after STEMI were divided among three subgroups: AF on the day of admission, AF 24-72 h and AF > 72 h after admission. Thirty-day mortality was assessed by telephone and via the municipal population registry. Twenty patients died < 30 days after admission. In 41 patients, AF was detected on the day of admission, in 14 patients 24-72 h after admission and in 18 patients > 72 h after admission. Mortality was higher in patients with AF on the day of admission (7.3 vs 2.2 %, p = 0.036) and 24-72 h after admission (14.3 vs 1.4 %, p < 0.001), but not in patients with AF > 72 h after admission (0 vs 1.1 %, p > 0.999). Age (odds ratio (OR) 1.123, p < 0.001), Killip class (adjusted OR 8.341, p < 0.001), AF on the day of admission (OR 3.585, p = 0.049) and 24-72 h after admission (OR 11.515, p = 0.003) were, amongst other variables, associated with an increased 30-day mortality. In conclusion, only new-onset incident AF during the first 72 h after admission was associated with 30-day mortality in STEMI patients.
| S-EPMC4547948 | biostudies-literature
Project description:BackgroundIt is somewhat controversial whether caffeine consumption is associated with an increased risk of developing atrial fibrillation (AF).ObjectiveWe prospectively assessed the relation between caffeine intake and incident AF.DesignA total of 33,638 initially healthy women who participated in the Women's Health Study and who were gt 45 y of age and free of cardiovascular disease and AF at baseline were prospectively followed for incident AF from 1993 to 2 March 2009. All women provided information on caffeine intake via food-frequency questionnaires at baseline and in 2004.ResultsDuring a median follow-up of 14.4 y (interquartile range: 13.8-14.8 y), 945 AF events occurred. Median caffeine intakes across increasing quintiles of caffeine intake were 22, 135, 285, 402, and 656 mg/d, respectively. Age-adjusted incidence rates of AF across increasing quintiles of caffeine intake were 2.15, 1.89, 2.01, 2.24, and 2.04 events, respectively, per 1000 person-years of follow-up. In Cox proportional hazards models updated in 2004 by using time-varying covariates, the corresponding multivariable-adjusted hazard ratios (95% CI) were 1.0, 0.88 (0.72, 1.06), 0.78 (0.64, 0.95), 0.96 (0.79, 1.16), and 0.89 (0.73, 1.09) (P for linear trend: 0.45). None of the individual components of caffeine intake (coffee, tea, cola, and chocolate) were significantly associated with incident AF.ConclusionsIn this large cohort of initially healthy women, elevated caffeine consumption was not associated with an increased risk of incident AF. Therefore, our data suggest that elevated caffeine consumption does not contribute to the increasing burden of AF in the population. This trial was registered at clinicaltrials.gov as NCT00000479.
| S-EPMC2921535 | biostudies-literature