Comparative analysis of the clinical features of nonvalvular atrial fibrillation among Tibetan, Han, and Hui patients in Qinghai Province, China.

BACKGROUND: Global nonvalvular AF rises, impacting health severely. In Qinghai, China's diverse setting, studying AF among varied ethnic groups is crucial OBJECTIVES: The purpose of this study was to compares cardiac features in AF among Tibetan, Han, and Hui patients to develop tailored prevention and treatment strategies for this region, the goal was to enhance the understanding of AF and provide an empirical basis for developing prevention and treatment strategies specific to this region METHODS: This study included a total of 3445 Tibetan, Han, and Hui patients diagnosed with nonvalvular atrial fibrillation and treated at the Qinghai Cardiovascular and Cerebrovascular Specialist Hospital, China, between January 2019 and January 2021. We analyzed the differences in cardiac structure, comorbidities, and other influencing factors among the different ethnic groups RESULTS: We found significant differences in gender, age, smoking history, lone atrial fibrillation, left heart failure, dilated cardiomyopathy, and diabetes between Tibetan, Han, and Hui patients (P < 0.05). Tibetan, Han, and Hui patients also differed with regard to left ventricular end-diastolic volume, left ventricular ejection fraction, fractional shortening, NT-proBNP, glycated hemoglobin, red blood cell distribution width, platelet count, platelet hematocrit, platelet distribution width, homocysteine (Hcy), C-reactive protein, and superoxide dismutase (SOD) (P < 0.05) CONCLUSION: Our study revealed variations in comorbidities, cardiac structure, and blood indexes among Tibetan, Han, and Hui AF patients, highlighting distinct patterns in complications and biomarker levels across ethnic groups.

Left ventricular hypertrophy phenotype to predict incident atrial fibrillation: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIM: Left ventricular hypertrophy (LVH) has been shown to be associated with the occurrence of atrial fibrillation (AF). However, the predictive value of the LVH phenotype for incident AF remains uncertain. This study aimed to investigate the predictive value of LVH phenotype for incident AF. METHODS AND RESULTS: This study utilized the Multi-Ethnic Study of Atherosclerosis (MESA) data. LVH was defined by cardiac magnetic resonance measured LV mass index. Isolated LVH was determined as LVH without elevated cardiac biomarker and malignant LVH was determined as LVH with at least 1 elevated biomarker. Receiver-operating characteristic (ROC) analysis was performed to calculate areas under the curves (AUC) for predicting AF. A total of 4983 community-dwelling participants were included, with a mean age of 61.5 years. 279 (5.6 %) had isolated LVH, and 222 (4.5 %) had malignant LVH. During a median follow-up of 8.5 years, 272 incident AF was observed. Compared to participants without LVH and elevated cardiac biomarkers, those with isolated LVH (HR, 1.82; 95 % CI, 1.03-3.20) and malignant LVH (HR, 4.13; 95 % CI, 2.77-6.16) had a higher risk of incident AF. Malignant LVH carried a 1.5-fold increased risk of AF compared to isolated LVH (HR: 2.48, 95 % CI: 1.30-4.73). Including the LVH phenotype in the CHARGE-AF model improved model discrimination (AUC increase: 0.03, p < 0.001). CONCLUSIONS: The risks of AF incidence varied across LVH phenotypes. Malignant LVH carried the highest risk among LVH phenotypes. LVH phenotype provides incremental predictive value over the variables included in the CHARGE-AF model.

Racial Differences in Atrial Fibrillation Management Between White Patients and Black Patients in Transthyretin Cardiac Amyloid.

Black patients have higher rates of stroke than White patients. Paradoxically, atrial fibrillation (AF) affects twice as many White patients compared with Black patients. Transthyretin cardiac amyloidosis (ATTR-CA) is associated with both AF and strokes. We hypothesized that although Black patients with ATTR-CA have a lower incidence of AF, when diagnosed with AF, they have increased thromboembolic events. Patients with ATTR-CA (n = 558) at 3 international centers were retrospectively identified. We compared baseline characteristics, presence of AF, outcomes of thromboembolism (stroke, transient ischemic attack, and peripheral embolism), major bleed, and mortality by race. Of all patients, 367 of 488 White patients (75%) were diagnosed with AF compared with 39 of 70 Black patients (56%) (p = 0.001). Black patients with AF had a hazard ratio of 5.78 (95% confidence interval 2.30 to 14.50) for time to first thromboembolic event compared with White patients. There were no racial differences in major bleeding. Black patients with AF more often lacked anticoagulation (p = 0.038) and had higher incidence of labile international normalized ratio (p <0.001). In conclusion, these data suggest that although Black patients with ATTR-CA have lower incidence of AF, they have increased thromboembolic events compared with White patients. These findings may be related to treatment discrepancies, time in therapeutic range for warfarin, and disparities in healthcare.

Racial and Ethnic Considerations in Patients With Atrial Fibrillation: JACC Focus Seminar 5/9.

Atrial fibrillation (AF) affects at least 60 million individuals globally and is associated with substantial impacts on morbidity, mortality, and health care expenditures. This review focuses on how race and ethnicity influence AF epidemiology, risk prediction, treatment, and outcomes; knowledge gaps in these areas are identified. Most AF studies have predominantly included White populations, with an underrepresentation of racial and ethnic groups, including but not limited to Black, Hispanic, and Indigenous individuals. Enhancement and implementation of AF risk prediction, prevention, and management call for studies that will gather accurate race-based epidemiologic data and evaluate social determinants and genetic factors in the context of multiple races and ethnicities. Available studies highlight inequities in access to treatment as well as outcomes between White individuals and persons of other races/ethnicities. These inequities will need to be addressed by a renewed emphasis on structural and social determinants of health that contribute to AF.

Multiple Blood Biomarkers and Stroke Risk in Atrial Fibrillation: The REGARDS Study.

Background Atrial fibrillation is associated with increased stroke risk; available risk prediction tools have modest accuracy. We hypothesized that circulating stroke risk biomarkers may improve stroke risk prediction in atrial fibrillation. Methods and Results The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study is a prospective cohort study of 30 239 Black and White adults age ≥45 years. A nested study of stroke cases and a random sample of the cohort included 175 participants (63% women, 37% Black adults) with baseline atrial fibrillation and available blood biomarker data. There were 81 ischemic strokes over 5.2 years in these participants. Adjusted for demographics, stroke risk factors, and warfarin use, the following biomarkers were associated with stroke risk (hazard ratio [HR]; 95% CI for upper versus lower tertile): cystatin C (3.16; 1.04-9.58), factor VIII antigen (2.77; 1.03-7.48), interleukin-6 (9.35; 1.95-44.78), and NT-proBNP (N-terminal B-type natriuretic peptide) (4.21; 1.24-14.29). A multimarker risk score based on the number of blood biomarkers in the highest tertile was developed; adjusted HRs of stroke for 1, 2, and 3+ elevated blood biomarkers, compared with none, were 1.75 (0.57-5.40), 4.97 (1.20-20.5), and 9.51 (2.22-40.8), respectively. Incorporating the multimarker risk score to the CHA2DS2VASc score resulted in a net reclassification improvement of 0.34 (95% CI, 0.04-0.65). Conclusions Findings in this biracial cohort suggested the possibility of substantial improvement in stroke risk prediction in atrial fibrillation using blood biomarkers or a multimarker risk score.

Screening for Atrial Fibrillation in American Indian Adults in a Tribal Primary Care Clinic.

Background American Indian adults have a higher risk of atrial fibrillation (AF) compared with other racial groups. We implemented opportunistic screening to detect silent AF in American Indian adults attending a tribal health system using a mobile, single-lead ECG device. Methods and Results American Indian patients aged ≥50 years followed in a tribal primary care clinic with no history of AF underwent a 30-second ECG. A cardiologist overread all tracings to confirm the diagnosis of AF. After AF was confirmed, patients were referred to their primary care physician for initiation of anticoagulation. Patients seen over the same time period, who were not undergoing screening, served as controls. A total of 1019 patients received AF screening (mean age, 61.5±8.9 years, 62% women). Age and sex distribution of those screened was similar to the overall clinic population. New AF was diagnosed in 15 of 1019 (1.5%) patients screened versus 4 of 1267 (0.3%) patients who were not screened (mean difference, 1.2%; 95% CI, 0.3%-2.2%, P=0.002). Eight of 15 with new screen-detected AF were aged <65 years. Those with screen-detected AF were slightly older and had a higher CHA2DS2-VASc score than those without AF. Fourteen of 15 patients diagnosed with new AF had a CHA2DS2-VASc score ≥1 and initiated anticoagulation. Conclusions Opportunistic, mobile single-lead ECG screening for AF is feasible in tribal clinics, and detects more AF than usual care, leading to appropriate initiation of anticoagulation. AF develops at a younger age in American Indian adults who would likely benefit from earlier AF screening. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03740477.

Incident Strokes Among American Indian Individuals With Atrial Fibrillation.

BACKGROUND American Indian individuals experience a relatively high risk for cardiovascular disease and have exhibited a higher risk of stroke compared with other racial and ethnic minorities. Although this population has the highest incidence of atrial fibrillation (AF) compared with other groups, the relationship between AF and nonhemorrhagic stroke among American Indian individuals compared with other groups has not been thoroughly studied. METHODS and RESULTS We used the Healthcare Cost and Utilization Project to evaluate risk of nonhemorrhagic stroke among American Indian individuals, with comparisons to White, Black, Hispanic, and Asian individuals, among all adult California residents receiving care in an emergency department, inpatient hospital unit, or ambulatory surgery setting from 2005 to 2011. Of 16 951 579 patients followed for a median 4.1 years, 105 822 (0.6%) were American Indian. After adjusting for age, sex, income level, insurance payer, hypertension, diabetes mellitus, coronary artery disease, congestive heart failure, cardiac surgery, valvular heart disease, chronic kidney disease, smoking, obstructive sleep apnea, pulmonary disease, and alcohol use, American Indian individuals with AF exhibited the highest risk of nonhemorrhagic stroke when compared with either non-American Indian individuals with AF (hazard ratio, 1.38; 95% CI, 1.23-1.55; P<0.0001) or to each race and ethnicity with AF. American Indian individuals also experienced the highest overall risk for stroke, with no evidence that AF disproportionately heightened that risk in interaction analyses. CONCLUSIONS American Indian individuals experienced the highest risk of nonhemorrhagic stroke, whether in the presence or absence of AF. Our findings likely suggest an opportunity to further study, if not immediately address, guideline-adherent anticoagulation prescribing patterns among American Indian individuals with AF.

Atrial Fibrillation in Indigenous Australians: A Multisite Screening Study Using a Single-Lead ECG Device in Aboriginal Primary Health Settings.

BACKGROUND: Circulatory diseases continue to be the greatest cause of mortality for Australian Aboriginal and Torres Strait Islander people, and a major cause of persistently lower life expectancy compared with non-Aboriginal Australians. The limited information that exists on atrial fibrillation (AF) prevalence in Aboriginal and Torres Strait Islander communities is mostly based on hospital admission data. This shows AF as principal or additional admission diagnosis was 1.4 times higher compared to non-Aboriginal Australians, a higher incidence of AF across the adult life span after age 20 years and a significantly higher prevalence among younger patients. Our study estimates the first national community prevalence and age distribution of AF (including paroxysmal) in Australian Aboriginal people. A handheld single-lead electrocardiograph (ECG) device (iECG), known to be acceptable in this population, was used to record participant ECGs. METHODS: This co-designed, descriptive cross-sectional study was conducted in partnership with 16 Aboriginal Community Controlled Health organisations at their facilities and/or with their services delivered elsewhere. The study was also conducted at one state community event. Three (3) Australian jurisdictions were involved: New South Wales, Western Australia and the Northern Territory. Study sites were located in remote, regional and urban areas. Opportunistic recruitment occurred between June 2016 and December 2017. People <45 years of age were excluded. RESULTS: Thirty (30) of 619 Aboriginal people received a 'Possible AF' and 81 an 'Unclassified' result from a hand-held smartphone ECG device. A final diagnosis of AF was made in 29 participants (4.7%; 95%CI 3.0-6.4%), 25 with known AF (five paroxysmal), and four with previously unknown AF. Three (3) of the four with unknown AF were aged between 55-64 years, consistent with a younger age of AF onset in Aboriginal people. Estimated AF prevalence increased with age and was higher in those aged >55 years than the general population (7.2% compared with 5.4%). Slightly more men than women were diagnosed with AF. CONCLUSIONS: This study is a significant contribution to the evidence which supports screening for AF in Aboriginal and Torres Strait Islander people commencing at a younger age than as recommended in the Australian guidelines (>65 years). We recommend the age of 55 years. Consideration should be given to the inclusion of AF screening in the Australian Government Department of Health annual 'Aboriginal and Torres Strait Islander Health Assessment'. CLINICAL TRIAL REGISTRATION: ACTRN12616000459426.

Persistent Asthma Is Associated With Increased Risk for Incident Atrial Fibrillation in the MESA.

BACKGROUND: Asthma and atrial fibrillation (AF) share an underlying inflammatory pathophysiology. We hypothesized that persistent asthmatics are at higher risk for developing AF and that this association would be attenuated by adjustment for baseline markers of systemic inflammation. METHODS: The MESA (Multi-Ethnic Study of Atherosclerosis) is a prospective longitudinal study of adults free of cardiovascular disease at baseline. Presence of asthma was determined at exam 1. Persistent asthma was defined as asthma requiring use of controller medications. Intermittent asthma was defined as asthma without use of controller medications. Participants were followed for a median of 12.9 (interquartile range, 10-13.6) years for incident AF. Multivariable Cox regression models were used to assess associations of asthma subtype and AF. RESULTS: The 6615 participants were a mean (SD) 62.0 (10.2) years old (47% male, 27% black, 12% Chinese, and 22% Hispanic). AF incidence rates were 0.11 (95% CI, 0.01-0.12) events/10 person-years for nonasthmatics, 0.11 (95% CI, 0.08-0.14) events/10 person-years for intermittent asthmatics, and 0.19 (95% CI, 0.120.49) events/10 person-years for persistent asthmatics (log-rank P=0.008). In risk-factor adjusted models, persistent asthmatics had a greater risk of incident AF (hazard ratio, 1.49 [95% CI, 1.03-2.14], P=0.03). IL (Interleukin)-6 (hazard ratio, 1.26 [95% CI, 1.13-1.42]), TNF (tumor necrosis factor)-α receptor 1 (hazard ratio, 1.09 [95% CI, 1.08-1.11]) and D-dimer (hazard ratio, 1.10 [95% CI, 1.02-1.20]) predicted incident AF, but the relationship between asthma and incident AF was not attenuated by adjustment for any inflammation marker (IL-6, CRP [C-reactive protein], TNF-α R1, D-dimer, and fibrinogen). CONCLUSIONS: In a large multiethnic cohort with nearly 13 years follow-up, persistent asthma was associated with increased risk for incident AF. This association was not attenuated by adjustment for baseline inflammatory biomarkers.

Evaluation of Risk Prediction Models of Atrial Fibrillation (from the Multi-Ethnic Study of Atherosclerosis [MESA]).

Atrial fibrillation (AF) is prevalent and strongly associated with higher cardiovascular disease (CVD) risk. Machine learning is increasingly used to identify novel predictors of CVD risk, but prediction improvements beyond established risk scores are uncertain. We evaluated improvements in predicting 5-year AF risk when adding novel candidate variables identified by machine learning to the CHARGE-AF Enriched score, which includes age, race/ethnicity, height, weight, systolic and diastolic blood pressure, current smoking, use of antihypertensive medication, diabetes, and NT-proBNP. We included 3,534 participants (mean age, 61.3 years; 52.0% female) with complete data from the prospective Multi-Ethnic Study of Atherosclerosis. Incident AF was defined based on study electrocardiograms and hospital discharge diagnosis ICD-9 codes, supplemented by Medicare claims. Prediction performance was evaluated using Cox regression and a parsimonious model was selected using LASSO. Within 5 years of baseline, 124 participants had incident AF. Compared with the CHARGE-AF Enriched model (c-statistic, 0.804), variables identified by machine learning, including biomarkers, cardiac magnetic resonance imaging variables, electrocardiogram variables, and subclinical CVD variables, did not significantly improve prediction. A 23-item score derived by machine learning achieved a c-statistic of 0.806, whereas a parsimonious model including the clinical risk factors age, weight, current smoking, NT-proBNP, coronary artery calcium score, and cardiac troponin-T achieved a c-statistic of 0.802. This analysis confirms that the CHARGE-AF Enriched model and a parsimonious 6-item model performed similarly to a more extensive model derived by machine learning. In conclusion, these simple models remain the gold standard for risk prediction of AF, although addition of the coronary artery calcium score should be considered.

Efficacy and safety of cryoballoon ablation for Chinese patients over 75 years old: A comparison with a younger cohort.

INTRODUCTION: Cryoballoon ablation (CBA) results in satisfactory outcomes for drug-resistant atrial fibrillation (AF) patients. However, the efficacy and safety of CBA have not yet been tested in the Chinese elderly population. Therefore, this study compared the recurrence of AF and complications of CBA in patients ≥75 years and <75 years. METHODS: A total of 677 patients (<75 years, n = 550; ≥ 75 years, n = 127) with paroxysmal (n = 603) or persistent (n = 74) non-valvular drug-resistant AF were included. The efficacy was assessed by the recurrence of AF, and the safety was evaluated by peri- and post-procedural complications. RESULTS: The CHA2DS2-VASc (2.6 ± 1.7 vs 4.8 ± 1.6, P < .01) and HAS-BLED (1.8 ± 0.8 vs 2.0 ± 0.8, P = .01) scores were significantly higher in the elderly group. The instant pulmonary vein isolation success rate was comparable (99.11% younger vs 98.98% older, P = .99). After a mean follow-up time of 12.8 ± 9.6 months, the 1-year freedom from AF rate was 80.6% vs 85.8% in the older and younger groups, respectively, while the survival analysis showed a nonsignificant difference in the rate of freedom from AF (log-rank P = .46). Cox regression showed that age was not a predictive factor for AF recurrence and was not dichotomized (hazard ratio [HR] = 0.868, 95% confidence interval [CI] 0.509-1.481; P = .6046) or continuous (HR = 0.990, 95% CI, 0.968-1.012, P = .3642). Similar complications rates were observed, including stroke (1.0% younger vs 0.93% older, P = .95) and major hemorrhagic events (1.2% younger vs 0% elder, P = .25). CONCLUSIONS: The efficacy and safety profiles of CBA in patients older than 75 years are comparable with those in younger patients.

Effects of Polymorphisms in Pre-miRNA on Inflammatory Markers in Atrial Fibrillation in Han Chinese.

BACKGROUND: MicroRNA molecules have been identified to play key roles in a broad range of physiological and pathological processes. Polymorphisms in the corresponding sequence space are likely to make a significant con-tribution to phenotypic variation. The aim of this study was to evaluate the pre-miR-146a C/G (rs2910164) and pre-miR-499 T/C (rs3746444) polymorphisms and their putative association with inflammatory markers in AF in Han Chinese. METHODS: A total of 123 participants were enrolled, 65 AF patients were confirmed with electrocardiogram (ECG) or dynamic electrocardiography, 58 normal individuals were assigned to the control group. RESULTS: Genotypes of the pre-miR-146a C/G (rs2910164) and pre-miR-499 T/C (rs3746444) polymorphisms were distinguished using the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The distribution of the pre-miR-146a C/G (rs2910164) genotypes CC, CG, and GG was 33.85%, 52.31%, and 13.84% in the AF group and 37.93%, 51.72%, and 10.35% in the controls, respectively. There was no significant difference in either genotype frequency distributions (p = 0.7973) or allele frequency distributions (p = 0.5411) between these two groups. The distribution of the pre-miR-499 T/C (rs3746444) genotypes TT, TC, and CC was 72.41%, 22.41%, and 5.18% in the controls and 49.23%, 38.46%, and 12.31% in AF subjects, respec-tively (p = 0.0296). The frequency of the C allele in the AF group was significantly higher than that in the control group (31.54% vs. 16.38%, p = 0.0057). Compared with the TT genotype, the C allele carriers (TC+CC genotypes) had a 2.7070-fold increased risk of AF. After being adjusted for age, gender, leucocytes, left atrial dimension, left ventricular ejection fraction, serum levels of lipids, and inflammatory markers, the association persisted (adjusted OR = 2.3387, 95% CI =1.1094 - 4.9300, p = 0.0280). Individuals with TC+CC genotype in pre-miR-499 T/C (rs3746444) had greater serum levels of IL-6 and hs-CRP than did patients with the TT genotype. CONCLUSIONS: Our data support that the pre-miR-499 T/C (rs3746444) polymorphism is associated with AF, and the C allele has increased risk for AF in Han Chinese.

Prevalence of atrial fibrillation and association with clinical, sociocultural, and ancestral correlates among Hispanic/Latinos: The Hispanic Community Health Study/Study of Latinos.

BACKGROUND: Hispanics/Latinos represent the largest ethnic minority group in the United States. Atrial fibrillation (AF) is the most common cardiac arrhythmia in the United States. OBJECTIVE: The purpose of this study was to provide data on the prevalence of AF and its correlates in a representative Hispanic/Latino population-based sample inclusive of all background groups. METHODS: Hispanic Community Health Study/Study of Latinos participants (n=16,415; 60% women; 59% age >45 years) were enrolled between March 2008 and June 2011, representing individuals of Cuban, Dominican, Mexican, Puerto Rican, Central American, and South American heritage. AF was defined by the 12-lead electrocardiogram and/or participant self-report of a physician diagnosis. Hispanic background-specific AF prevalence rates were determined. Weighted sequential logistic regression models were adjusted for demographic factors (age and sex) and clinical variables (diabetes, hypertension, body mass index, tobacco use, and estimated glomerular filtration rate). RESULTS: The overall weighted prevalence of AF was 1.0% (n=162), with the highest prevalence in Hispanics of Dominican and Puerto Rican backgrounds (1.9% and 2.5% respectively) and the lowest in those of Mexican background (0.3%). Diabetes, hypertension, renal disease, left ventricular hypertrophy determined by the electrocardiogram, alcohol use, and English language preference (greater acculturation) (P < .01 for all) were significantly associated with higher AF prevalence. Multivariate analysis by Hispanic/Latino background group showed that Hispanics of Dominican and Puerto Rican backgrounds were at a 3- to 6-fold higher risk of AF than their Mexican counterparts. CONCLUSION: In a diverse representative population of Hispanics/Latinos, overall AF prevalence was low and varied significantly across Hispanic/Latino background groups independent of clinical or demographic factors.

Yield and consistency of arrhythmia detection with patch electrocardiographic monitoring: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Patch electrocardiographic (ECG) monitors permit extended noninvasive ambulatory monitoring. To guide use of these devices, information is needed about their performance. We sought to determine in a large general population sample the acceptability of patch ECG monitors, the yield of arrhythmia detection, and the consistency of findings in participants monitored twice. METHODS: In the Multi-Ethnic Study of Atherosclerosis, 1122 participants completed one or two monitoring episodes using the Zio Patch XT, a single-channel ECG patch monitor capable of recording for 14 days. Recordings were analyzed for atrial fibrillation (AF), atrial flutter, atrioventricular block, pauses, and supraventricular and ventricular ectopy. RESULTS: The mean(SD) age at the time of monitoring was 75(8) years, 52% were men, and 15% had a prior history of clinically-recognized AF/flutter. The median monitoring duration was 13.8 days. Among 804 participants with no prior clinical history of AF/flutter and at least 12 days of monitoring on a single device, AF/flutter was detected in 32 (4.0%); in 38% of these, AF/flutter was first detected during days 3 through 12 of monitoring. In participants monitored twice, findings from the two devices showed excellent agreement for supraventricular and ventricular ectopic beats per hour, but only fair agreement for high-grade atrioventricular block and pauses of >3 s duration. CONCLUSIONS: In a general population of older individuals, new diagnoses of AF/flutter were made in 4.0% of participants without a prior history. A single monitoring episode accurately estimated rates of supraventricular and ventricular ectopy.

Collagen Biomarkers and Incidence of New Onset of Atrial Fibrillation in Subjects With No Overt Cardiovascular Disease at Baseline: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Atrial fibrosis is a hallmark of structural remodeling in atrial fibrillation (AF). Plasma procollagen type III N-terminal propeptide (PIIINP) reflects collagen synthesis and degradation while collagen type I carboxy-terminal telopeptide (ICTP) reflects collagen degradation. We aimed to study baseline plasma PIIINP and ICTP and their associations with incident AF in participants initially free of overt cardiovascular disease. METHODS: In a stratified sample of the Multi-Ethnic Study of Atherosclerosis, initially aged 45-84 years, 3071 participants had both PIIINP and ICTP measured at baseline. Incident AF in 10-year follow-up was based on a hospital International Classification of Diseases code for AF or atrial flutter, in- or outpatient Medicare claims through 2011 (primarily in those aged 65-84 years), or ECG 10 years after baseline (n=357). The associations of PIIINP and ICTP with incident AF were estimated using Poisson regression with follow-up time offset. RESULTS: Baseline PIIINP (5.50±1.55 µg/L) and ICTP (mean±SD, 3.41±1.37 µg/L) were positively related (both P<0.0001) to incident AF in a model adjusting for age, race/ethnicity, and sex, with an apparent threshold (relative incidence density 2.81 [1.94-4.08] for PIIINP ≥8.5 µg/L [3.5% of the sample] and 3.46 [2.36-5.07] for ICTP ≥7 µg/L [1.7% of the sample]). Findings were attenuated but remained statistically significant after further adjustment for systolic blood pressure, height, body mass index, smoking, and renal function. Additional adjustment for other risk factors and biomarkers of inflammation did not alter conclusions. CONCLUSIONS: Plasma collagen biomarkers, particularly at elevated levels, were associated with excess risk for AF.

Atrial fibrillation in an African-American cohort: The Jackson Heart Study.

BACKGROUND: Atrial fibrillation (AF) is an important public health problem across race/ethnic groups. Data from US cohort studies initiated in the 1980s suggest a higher prevalence of AF risk factors among African-Americans (AAs) than whites, but lower AF incidence. The Jackson Heart Study (JHS) is a community-based study of 5306 AAs recruited starting in 2000. HYPOTHESIS: Demographic, anthropometric, cardiovascular, and/or electrocardiographic factors are associated with AF incidence in JHS. METHODS: Using baseline participant characteristics and incident AF identified through hospital surveillance, study electrocardiogram, and Medicare claims, we estimated age- and sex-specific AF incidence rates, compared them with rates in AA participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and Cardiovascular Health Study (CHS), and examined associations of cardiovascular risk factors with AF. RESULTS: A total of 66 participants had prevalent AF at baseline. Over an average follow-up of 8.5 years, 242 cases of incident AF were identified. Age- and sex-specific AF incidence rates in JHS were similar to those among AAs in MESA and appeared slightly lower than those among AAs in CHS. In an age- and sex-adjusted model, associations with incident AF were observed for modifiable risk factors: high body weight (HR = 1.23 per 15 kg, 95%CI 1.13-1.35), systolic blood pressure (HR = 1.29 per 20 mmHg, 95%CI 1.13-1.47), and current smoking (HR = 1.80, 95%CI 1.27-2.55). Risk estimates associated with these risk factors were only slightly attenuated after multivariable adjustments. CONCLUSIONS: These findings underscore the potential additional benefits of interventions for weight management, control of hypertension, and smoking cessation for the prevention of AF among AAs.

Life's Simple 7 and the risk of atrial fibrillation: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: We examined the association between the American Heart Association's Life's Simple 7 (LS7) metrics and the risk of atrial fibrillation (AF) in the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective cohort study of adults free of cardiovascular disease (CVD) at baseline. METHODS: We analyzed data from 6506 participants. The LS7 metrics (smoking, physical activity, body mass index, diet, blood pressure, total cholesterol and blood glucose) were each categorized into ideal (assigned 2 points), intermediate (1 point) or poor (0 points). Scores were summed for a maximum of 14. A score of 0-8 was considered inadequate; 9-10, average and 11-14, optimal for cardiovascular health. Atrial fibrillation was ascertained using ICD-9 codes from hospital discharge records and Medicare claims data. Cox proportional hazard ratios (HR) and incidence rates of AF per 1000 person-years were calculated. RESULTS: During a median follow-up of 11.2 years (interquartile range: 10.6-11.7 years), 709 (11%) participants were hospitalized with a first AF episode. In the overall cohort, optimal scores at baseline were associated with a 27% lower risk for AF compared with inadequate scores (0.73 [0.59-0.91]). A similar finding was observed when the results were stratified by race/ethnicity (White, Chinese American, African American and Hispanic), though many of the associations were not statistically significant. There was no interaction by race/ethnicity (p = 0.15). CONCLUSIONS: In the overall cohort, optimal LS7 status was associated with a lower risk of AF. These findings suggest that promoting ideal cardiovascular health may reduce the incidence and burden of AF.

Population pharmacokinetics and pharmacogenomics of apixaban in Japanese adult patients with atrial fibrillation.

AIMS: This study aimed to analyse the effects of genetic polymorphisms in drug transporters and metabolizing enzymes, and clinical laboratory data on the pharmacokinetic parameters of apixaban. METHODS: Data were collected from 81 Japanese patients with atrial fibrillation. Pharmacogenomic data were stratified by ABCB1, ABCG2 and CYP3A5 polymorphisms. The pharmacokinetic profile of apixaban was described by a one-compartment model with first-order absorption. Population pharmacokinetic analysis was conducted using a nonlinear mixed effect modelling (NONMEM™) program. RESULTS: The nonlinear relationship between oral clearance (CL/F) of apixaban and creatinine clearance (Ccr) was observed. The population mean of CL/F for a typical patient (Ccr value of 70 ml min-1 ) with the CYP3A5*1/*1 and ABCG2 421C/C or C/A genotypes was estimated to be 3.06 l h-1 . When Ccr values were set to the typical value, the population mean of CL/F was 1.52 times higher in patients with the CYP3A5*1/*1 genotype compared with patients with the CYP3A5*1/*3 or *3/*3 genotype, while the population mean of CL/F was 1.49 times higher in patients with the ABCG2 421C/C or C/A genotype compared with patients with the ABCG2 421A/A genotype. However, no covariates affected the population mean of the apparent volume of distribution (Vd/F) of apixaban. The population mean of Vd/F was estimated to be 24.7 l. CONCLUSION: The present study suggests that the ABCG2 421A/A and CYP3A5*3 genotypes and renal function are intrinsic factors affecting apixaban pharmacokinetics. These findings may provide useful information for precision medicine using apixaban, to avoid the risk of adverse reactions.

Usefulness of the American Heart Association's Life Simple 7 to Predict the Risk of Atrial Fibrillation (from the REasons for Geographic And Racial Differences in Stroke [REGARDS] Study).

The American Heart Association has identified metrics of ideal cardiovascular (CV) health known as Life's Simple 7 (LS7). We determined the prospective relationship between the LS7 and the incident atrial fibrillation (AF) in a biracial cohort. The REasons for Geographic And Racial Differences in Stroke (REGARDS) study enrolled non-Hispanic black and white adults 45 years or older. This analysis included 9,576 REGARDS participants (mean age 63 ± 8.4 years; 57% women; 30% black) who were free of AF at baseline and completed a follow-up examination 9.4 years later. An overall LS7 score was calculated at baseline as the sum of the LS7 component scores and classified as inadequate (0 to 4), average (5 to 9), or optimal (10 to 14) CV health. The primary outcome was incident AF, identified at follow-up by either electrocardiogram or a self-reported medical history of a physician diagnosis. A total of 725 incident AF cases were detected. Compared with the inadequate category (n = 534), participants in the optimal category (n = 1,953) had a 32% lower odds of developing AF (odds ratio 0.68; 95% confidence interval 0.47, 0.99) in a logistic regression model adjusted for demographic characteristics, alcohol use, left ventricular hypertrophy, coronary heart disease, and stroke. A 1-point higher LS7 score was associated with a 5% lower odds of incident AF (odds ratio = 0.95; 95% confidence interval 0.91, 0.99). In conclusion, better CV health, as defined by the LS7 score, is associated with a reduction in development of AF.