Ethnic Differences in the Risk and Outcomes of Atrial Fibrillation

Corresponding Author

Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide expected to affect 6 to 12 million people by 2050, and the number of adults over 55 years with AF will double from 2010 to 2060 in Europe.^1,2 AF is associated with a 4- to 5-fold increased risk of stroke.³ Racial and ethnic differences in AF risk within the United States have been noted with studies suggesting that White individuals have a higher risk of AF compared with under-represented racial-ethnic groups (UREG), including Black, Hispanic, American Indian, Alaska Native, and South Asian individuals.4, 5, 6 Despite a lower incidence of AF among UREG, these groups appear to experience a higher rate of AF-related ischemic strokes compared with White individuals.⁷

The mechanisms underlying these racial and ethnic differences in the risk and outcomes of AF may be complex, involving a combination of genetic factors, differential access to health care, and broader social determinants of health. In the United States, health care access may vary significantly across different UREG, potentially contributing to differences in diagnosing and treating AF. In contrast, the United Kingdom has a socialized system that provides equal access to health care and may provide clarity regarding whether and why racial and ethnic differences in AF risk and outcomes exist.

In this issue of JACC: Advances, Frimodt-Møller et al⁸ aimed to analyze population-based data on AF in the United Kingdom to gain insights into AF-related differences across different races and ethnicities. The authors queried the UK Biobank, a population-based prospective cohort study in which patients were enrolled from 2006 to 2010, to identify 458,785 participants eligible for this analysis. Ethnicity was self-identified as one of the following categories: White, Black, South Asian, Chinese, or multiracial (UREG), following UK National Health Service classifications. The study collected data on important demographic, clinical factors, individual variables like alcohol and tobacco use (which could be inter-related to social/community characteristics), ethnicity as well as social determinants of health such as education level.

They found that of 458,785 participants, 94.5% were White, and these people tended to be older, less educated, and consumed alcohol more frequently than their counterparts. They also had a higher prevalence of AF prior to recruitment (P < 0.001). South Asian individuals had a higher incidence of diabetes, hypertension, coronary artery disease, congestive heart failure, and kidney disease (1.5–4.0 times higher) compared with White individuals. During an average follow-up of 11.1 ± 1.7 years and after excluding patients with prior AF, 8,706 participants developed incident AF. Incident AF rates were significantly lower in UREG compared with White individuals. Incident strokes/systemic infarcts occurred in 1,550 individuals, with 1,513 being White and 37 from UREG. Multiracial individuals had a higher risk of ischemic stroke compared with White individuals (adjusted HR: 2.25; 95% CI: 1.01-5.04; P = 0.048). However, ethnicity was not significantly associated with the relationship between AF and ischemic stroke (P = 0.71).⁸

Similar to findings of studies in the United States, the highest AF risk in this analysis of the UK Biobank was among White individuals. That White individuals were older and more likely to consume alcohol than people of other ethnicities may have skewed the results because these factors have been shown to increase AF risk.⁹ Despite the fact that South Asian individuals had higher rates of several comorbidities, their AF rates were lower than those of White individuals, resembling the "AF-paradox" noted in Black individuals in the United States.¹⁰ There was no statistically significant difference in ischemic stroke/systemic infarct risk among different ethnicities in the United Kingdom, which contrasts with U.S. findings, where UREG have been found to have a higher risk of ischemic stroke.⁶ However, as the authors pointed out, the number of stroke and systemic infarct events in their study were likely too small to provide adequate statistical power for these comparisons. A sensitivity analysis suggested a higher risk of ischemic stroke among multiracial individuals compared with White individuals. This finding will need further investigations for validation and confirmation.

In interpreting the results of this study, important limitations, largely acknowledged by the authors, should be kept in mind. Population studies like the current study do not help establish causality, and despite the use of statistical methods that adjust for confounders, not all confounders were accounted for, and residual confounding is likely. There were no data on treatments received by patients for AF, and these therapies influence outcomes. Not all social determinants of health were considered for this analysis. There is the possibility of underreporting of AF, as continuous monitoring that yields more accurate data was not used. Differential use of monitoring across ethnic groups may account for differences in rates of detected AF.

While the study by Frimodt-Møller et al⁸ provides helpful observations, it leaves several questions unanswered. Is the higher risk of AF among White individuals than other ethnicities real? If so, what are the reasons for this difference? Potential reasons for this difference have been proposed that include genetic factors, differences in left atrial remodeling and scar burden, higher atrial natriuretic peptide levels, and more frequent nonpulmonary vein triggers which contribute to higher AF risk in White individuals of European ancestry.¹¹ However, these factors should be investigated more thoroughly in future studies. Do patients from UREG with AF have a higher risk of stroke than White patients? If so, what causes these differences in stroke? What about ethnic differences in other outcomes such as heart failure? What is the contribution of the different components of social determinants of health to the risk of AF and outcomes of AF? While the paper by Frimodt-Møller and colleagues elicits more questions than answers, it will hopefully help propel more research in this area.

Funding support and author disclosures

Dr Tamirisa is a speaker for Sanofi and Abbott. Dr Al-Khatib has reported that she has no relationships relevant to the contents of this paper to disclose.