Atrial Fibrillation in Middle Eastern Arabs and South Asians: Summary of Published Articles in the Arabian Gulf.

Seven studies are summarized herein focusing on different aspects of Atrial fibrillation (AF) in two unique ethnicities for which there is very limited literature published before; Middle Eastern Arabs and South Asians, using data from a national registry of cardiovascular diseases in Qatar over a 20-years period (1991-2010). These studies shed light upon important aspects of AF presentations and outcomes in these two ethnicities, thereby enriching the world literature on AF. In the process, several novel observations were reported and new questions were raised that warrant further investigations. Copyright:

INTRODUCTION

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice.[123] The epidemiology and clinical features of AF have primarily been characterized in whites of European-descent. Data about AF in other ethnicities is very limited.[456789] Herein, evidence from studies is presented focusing on different aspects of AF, including: etiologies; secular trends; cardiovascular risk factors; therapy; and outcome in two unique ethnicities that have not been adequately studied together previously (Middle Eastern Arabs and South Asians), using data from a national registry of cardiovascular diseases in Qatar - a Middle Eastern country with a population consisting mainly of Arabs and South Asians and making it ideal for population-based studies in these two ethnicities. The vast majority of Non-Arabs are South Asians mainly from India, Pakistan, Nepal and Bangladesh. The studies are based at Hamad General Hospital, Doha, Qatar. The Cardiology and Cardiovascular Surgery Database at Hamad General Hospital was used for these studies. Data are entered on all patients admitted to Hamad General Hospital with cardiac illnesses. The investigation was approved by Hamad Medical Review Board prior to data analysis. Data were collected from the clinical records written by physicians at the time of patient's discharge from the hospital according to predefined criteria for each data point. These records have been coded and registered at the cardiology department since January 1991. The research undertaken focused on several other aspects peculiar to the effects of AF in these two ethnicities. This included; religious fasting, gender differences, in patients with chronic kidney disease and acute myocardial infarction

Secular Trends, Treatments, and Outcomes of Middle Eastern Arab and South Asian Patients Hospitalized with Atrial Fibrillation: Insights from a 20-Year Registry in Qatar (1991–2010)

Salam AM, AlBinali HA, Al-Mulla AW, Singh R, Al Suwaidi J. Angiology 2013 Oct; 64 (7):498-504. doi: 10.1177/0003319712460332. PubMed PMID: 23028177.

Main findings

During the 20-years period; 2857 Arabs and 548 Asians were hospitalized for AF. Arabs were 9 years older (58 vs. 49, P < 0.001), with higher prevalence of hypertension (41.7% vs. 28.8%, P < 0.001) and diabetes mellitus (37.5% vs. 25.7%, P < 0.001), compared to Asians. Valvular heart disease and acute coronary syndromes were more common among Asians (6.8% vs. 3.7%; P < 0.001, and 9.9% vs. 6.9%; P = 0.02, respectively), while congestive heart failure was more common in Arabs (20% vs. 12.4%, P < 0.001). Overall in-hospital mortality was lower for Asians compared to Arabs (2.6% vs. 4.8%, P = 0.02), while stroke rates were comparable.

There were significant variations in the prevalence of underlying cardiac etiologies in both ethnicities, with an increase in ischemic heart disease and decrease in the prevalence of valvular heart disease in the latter years of the study but mortality trend was steady in both ethnic groups over the study period.

There was an increase in the prevalence of diabetes mellitus and hypertension in both groups in the latter years of the study period compared to earlier years but there was no change in mortality trends. There was a significant increase in the use of anticoagulants over the 20 years period from 17% to 44.1% in the overall cohort. Ethnicity was not an independent predictor of higher mortality when corrected for other predictors by Multivariate analysis.

Significance

Previous studies have suggested that the mortality and morbidity associated with AF was not homogeneous when taking into consideration underlying etiologies, related co-morbidities, complications, and treatment strategies. Given the improvements in the recognition and management of the co-morbid conditions associated with AF, especially hypertension, heart failure, and coronary artery disease, one would expect an improvement in the clinical outcome and prognosis.[1011] This was not the case as demonstrated by the steady rate of mortality and stroke over the 20 years of our study, although our analysis was limited to in hospital outcomes.

In addition, our study also highlights the suboptimal use of oral anticoagulation in patients with AF in spite of convincing evidence from large randomized trials showing that anticoagulation significantly reduces stroke rates in patients with AF. To the best of our knowledge the current study was the first ever report of comparative ethnic trends in etiologies and outcome of AF over a 20-year period.

Novelty

Most of the medical research has focused on the prevalence and incidence of AF in different populations and countries.[123] However, the literature is scarce in studies addressing secular trends in the incidence and subsequent mortality in a contemporary, nationally representative sample of different ethnicities.[39] The literature is particularly devoid from studies addressing that in Middle Eastern Arab and South Asian ethnicities which this study examined over a 20 year period.

Women Hospitalized with Atrial Fibrillation: Gender Differences, Trends and Outcomes from a 20-Year Registry in a Middle Eastern Country (1991–2010)

Salam AM, Al Binali HA, Al Mulla AW, Asaad N, Singh R, Al-Qahtani A, Al Suwaid J. Int J Cardiol 2013 Sep; 168 (2):975-80. Doi: 10.1016/j.ijcard.2012.10.041. Pubmed PMID: 23159409.

During the 20-years period; 1417 women and 2432 men were hospitalized for AF. Women were 5 years older (59 vs. 54, P < 0.001) and more likely to have diabetes mellitus (37.5% vs. 25.7%, P < 0.001) and hypertension (49.5% vs. 32.1%, P < 0.001), and were also less likely to be current smokers (1.3% vs. 18.9%, P < 0.001), and to have ischemic heart disease (8.3% vs. 12.3, P < 0.001), when compared to men. There was no gender preference in the use of anticoagulation. The prevalence of concomitant ischemic heart disease and hypertension increased, while the prevalence of valvular heart disease and heart failure decreased among patients hospitalized with AF over the study period. In-hospital mortality and stroke rates were not different between the two groups. The use of warfarin was significantly trending higher over the study period but no differences were found between men and women. Multivariate predictors of poor outcome among patients hospitalized with AF are age, diabetes mellitus and chronic renal impairment. Gender was not an independent predictor of poor outcome.

Healthcare in the third world countries have long been accused of being biased against women[12] particularly in the use of evidence-based treatment and consequently higher morbidity and mortality in women even when other risk factors are accounted for. The major evidence-based treatment in AF is stroke prevention therapy and our study showed equal use of anticoagulants and anti-platelets among both sexes in our patients. In addition, after correctly for other risk factors, female gender was not independently associated with poor outcome. Furthermore, the prevalence of diabetes mellitus was much higher than any previous reports. This is consistent with the high prevalence of diabetes mellitus in the Arab Middle east in general and in Qatar specifically[13] and may in part explain the relatively younger age of AF female patients among both Asian and Middle Eastern Arabs.

While there are an increasing number of studies addressing the issue of gender differences in cardiovascular disorders particularly coronary artery disease,[14] nonetheless, only few studies have dealt with gender differences and AF.[15161718]

Some studies suggested less favorable outcomes in women with higher relative mortality, a higher risk of stroke and an underuse of anticoagulants.[171819] However, results from these studies were inconsistent and included relatively small numbers of women over a short time period. Moreover, most of published studies were conducted in the developed world and included mainly Caucasian patients.

Data about women with AF among other ethnicities are very limited. The current study extended these observations in two unique ethnicities that have not been adequately studied previously; (Middle Eastern Arabs and South Asians), and reported for the first time secular trends of patients hospitalized with AF according to gender over a 20-years period.

Effect of Age on Treatment, Trends and Outcome of Patients Hospitalized with Atrial Fibrillation

Salam AM, AlBinali HA, Al-Sulaiti EM, Al-Mulla AW, Singh R, Al Suwaidi J. Effect of age on treatment, trends and outcome of patients hospitalized with atrial fibrillation: insights from a 20-years registry in a Middle-Eastern country (1991-2010). Aging Clin Exp Res. 2012 Dec;24(6):682-90. doi: 10.3275/8757. PubMed PMID: 23211770.

1345 patients were ≤50 years, 1759 were between >50 and 70 years and 744 patients were >70 years old. Elderly patients were more likely to have hypertension and chronic renal impairment. There was a higher prevalence of associated coronary artery disease and aortic stenosis in elderly patients with a lower left ventricular ejection fraction than the younger age groups. A lower use of anticoagulation in the elderly group was observed but there was no underuse of other evidence-based medications. The older age AF patients had significantly higher in-hospital mortality and stroke rates with no significant changes in mortality trends over the 20-years of study.

Secular trends analysis showed that the associated acute coronary syndromes, hypertension and diabetes mellitus prevalence were trending higher in the elderly group while heart failure prevalence was trending lower. There were no significant differences in mortality trends in the elderly group while stroke rate was higher. The use of warfarin as well as aspirin in the elderly group was significantly trending higher over the study period. Multivariate analysis of mortality predictors showed that increasing age was not an independent predictor of in-hospital mortality.

Under-utlization of oral anticoagulants (OAC) in the elderly group in this patient population is noted. This is quite alarming considering the overwhelming evidence supporting OAC for stroke prevention.[20] Nonetheless, the use of warfarin in the elderly group was significantly trending higher over the study period reflecting perhaps increasing awareness among treating physicians of its importance and indication. Reasons for under-utilization of OAC include physicians' underestimation to risk of stroke, overestimation of the risk of hemorrhagic complications, the frailty of elderly people, cognitive impairment, poor compliance of monitoring, falls risk, associated co-morbidity and concomitant medications which may, indeed, play a role.

The current study underscores the urgent need for prospective studies to investigate warfarin contraindications, relative warfarin efficacy and bleeding risks in our region to help guide healthcare providers in warfarin prescribing in this frail patient population and consequently reduce the risk of AF-related disabling strokes and mortality.

It has long been established that AF is a disease of aging with AF incidence doubling with each decade of life.[21] Studies have estimated that the annual incidence of AF per 1000 person-years to be 1.9 in women and 3.1 in men younger than 65 years, but exceeds 32 per 1000 person-years in patients 80 years and older. Age-related declines in vascular compliance, increased population longevity, and the increasing prevalence of cardiovascular disease in older persons has led to an expanding AF epidemic in the developed world.[2223242526]

However, most studies on AF epidemiology, treatment, and outcomes have been performed in North America and Europe involving mainly Caucasians patients and while there are recognized ethnic differences in cardiovascular risk profiles, the world literature on epidemiology of AF in different ethnicities is limited, particularly concerning elderly patients. Herein we studied the presentation, treatment and outcome of elderly patients aged above 70 years that were hospitalized with AF and compared them to younger age groups in a population of Middle Eastern Arabs and South Asians over a 20-years period.

The Prognostic Implications of Lack of Palpitations in Patients Hospitalized with Atrial Fibrillation

Salam AM, Gersh BJ, AlBinali HA, Singh R, Asaad N, Al-Qahtani A, Suwaidi JA. Int J Clin Pract 2014 Jan; 68 (1):122-9. doi: 10.1111/ijcp.12230. PubMed PMID: 24341306.

During the 20-years period, 3850 patients were hospitalized for AF; 1724 (44.8%) had palpitations on presentation while 2126 (55.2%) had no palpitations. Patients who lacked palpitations were 9 years older, had a higher prevalence of diabetes mellitus (64.7% vs. 35.3%), underlying coronary artery disease (14.6%, vs. 6.2%,) and severe left ventricular dysfunction on echocardiography (25.5% vs. 6.6%), (all, P value = 0.001). There were 141 deaths among the group with no palpitations compared with 19 among the group with palpitations (6.6% versus 1.1%). Multivariate analysis of mortality predictors identified -lack of palpitations- as an independent predictor of in-hospital mortality (relative risk 5.56; 95% confidence interval 1.20 – 25.0, P = 0.03).

The current study represents the largest observational study comparing the impact of symptoms at the presentation with AF on patient outcomes. The mortality rate of patients without palpitations was significantly higher compared to patients with palpitations. In addition, the study demonstrated for the first time that absence of palpitations was an independent predictor of in-hospital mortality. We suspect that this most likely could be due to confounders, which were significantly more frequent in these patients so that in patients who were admitted in acute coronary syndromes (ACS) or heart failure, the presence of other more severe symptoms may have overshadowed the presence of milder symptoms of palpitations.

Yet To the best of our knowledge the study was the first ever report demonstrating that -lack of palpitations- as predictor of mortality independent of other risk factors or therapy. Further research is warranted to confirm and explain the mechanisms behind this novel observation and to investigate the utility of this cost-effective prognostic indicator in risk stratification of patients with AF.

It is well recognized that the presentations of AF at the time of first diagnosis vary substantially with palpitations being the most common typical symptom. Other atypical symptoms include chest pain, shortness of breath (SOB) and dizziness.[27] In addition, about 15% to 30% of patients are asymptomatic.[28293031] It is sometimes practiced that when AF is thought to be suppressed, as evidenced by the absence of clinical symptoms and the presence of sinus rhythm on routine electrocardiograms, some physicians tend to stop anticoagulation in an effort to avoid the perceived unnecessary exposure of patients to anticoagulation therapy.[32]

Nonetheless, evidence from ambulatory external electrocardiogram monitoring and examining implanted device memories have demonstrated that such patients may have asymptomatic recurrences of AF and that these subclinical episodes expose them to the risk of ischemic stroke and other thromboembolic events,[333435] thereby questioning the utility of lack of symptoms as an indicator of lower risk. The aim of this study was to examine the prevalence and prognostic implications of lack of typical symptoms on presentation with AF, namely palpitations, among patients hospitalized with AF in a population of Middle Eastern Arabs and South Asians over a 20-years period.

Impact of Chronic Kidney Disease on the Presentation and Outcome of Patients Hospitalized with Atrial Fibrillation: Insights from Qatar

Salim I, Al Suwaidi J, AlBinali HA, Singh R, Al-Qahtani A, Asaad N, Salam AM. Angiology 2018 Mar; 69 (3):212-219. doi: 10.1177/0003319717717849. PubMed PMID: 28691505.

Out of 5201 AF patients; 264 (5.1%) had CKD. Compared with patients without CKD, CV risk factors were significantly more prevalent in CKD patients including hypertension, diabetes mellitus (DM), and old myocardial infarction whereas smoking was more prevalent in patients with normal renal function. Patients with CKD were significantly more likely to present with shortness of breath and chest pain compared with patients without CKD. Palpitation was significantly more common in patients with normal renal function.

Other cardiac diagnosis at the time of admission including ACS and heart failure were significantly more prevalent in CKD patients while there was no difference in valvular heart disease (P = 0.6). In patients who underwent echocardiography, left ventricular (LV) dysfunction was significantly more frequent in patients with CKD while normal LV ejection fraction was significantly more frequent in patients with normal renal function. In-hospital stay (mean ± SD) was significantly longer for patients with CKD compared with patients without CKD (6.3 ± 4.3 vs 4.5 ± 3.6 days, P = 0.001).

Compared with patients without CKD, patients with CKD had significantly higher crude in-hospital mortality (11.7 vs 4.0%, P = 0.001) and stroke (2.3- vs 0.3%, P = 0.001). On multivariate analysis, independent predictors of in-hospital mortality were: CKD [Odds Ratio (OR) 2.84; 95% confidence interval (CI) 1.33 to 6.08, P = 0.001], ACS [OR 2.97 (95% CI 1.67 to 5.30, P = 0.001)], left ventricular ejection fraction (LVEF) ≤40% [OR 2.44; 95% CI 1.41-4.35, P = 0.001] and DM [OR 1.96; 95% CI 1.03-3.70, P = 0.04].

The current study demonstrated that patients with CKD have different symptoms when presenting with AF compared to those with normal renal function. This finding suggests that these patients should be screened for the presence of AF particularly when the reason for deterioration is not evident, even in the absence of palpitations. Further research is required in order to reduce the high morbidity and mortality observed in this high risk group.

Patients with Chronic Kidney Disease (CKD) have a high prevalence of cardiovascular disorders (CVD) which is responsible for most of the morbidity and mortality associated with CKD rather than progression to end stage renal failure.[3637] Furthermore, most of the available literature describe AF in cohorts of patients with CKD showing high prevalence and incidence and associated higher morbidity and mortality.[3839404142] Yet, the clinical characteristics and outcome of patients who are hospitalized with AF and coexistent CKD have rarely been reported.

In this study, the clinical presentation, management and outcomes of patients hospitalized with AF, with and without co-existent CKD, in a population of Middle Eastern Arabs and South Asians over a 20-years period was examined.

Atrial Fibrillation in Middle-eastern Arab and South Asian Patients Hospitalized with Acute Myocardial Infarction (1991–2010): Experience from a 20-Year Registry in Qatar

Salam AM, Al BH, Singh R, Gehani A, Asaad N, Al-Qahtani A, Suwaidi JA. Acta Cardiol 2013 Apr; 68 (2):173-80. PubMed PMID: 23705560.

During the 20-years period; a total of 12881 patients were hospitalized with AMI of these 5028 were Arabs and 5985 were South Asians. A total of 227 had AF during hospitalization with an overall incidence of 1.8% (156 Arabs; incidence 3.1% and 48 South Asians; incidence 0.8%). The mean age of AF patients was 65 years (Arabs 69, South Asians 54). Patients with AF were significantly older and had more cardiovascular co-morbidities compared to patients without AF, and were more likely to have Non-ST elevation AMI on presentation. Patients with AF had significantly higher in-hospital mortality rate (20.3% versus 7.1%; P = 0.001) and stroke rates (1.8% versus 0.3%; P = 0.001) when compared to patients without AF. Age was the only independent predictor of AF development in patient with AMI in our study.

This study reported an overall incidence of 1.8% of AF in AMI patients which is lower than that observed in other studies performed in North America and Europe which showed an incidence ranging from 6% to 15% depending on the cohort of AMI studied.[4344] Sub-analysis according to ethnicity revealed an incidence of 0.8% in South Asians. This very low frequency observed in South Asians is concordant with earlier observations in this ethnicity. We also report an incidence of 3.1% in Arabs in our cohort. This is consistent with our previous observation from the second Gulf Registry of Acute Coronary Events (Gulf RACE-2) analysis,[45] which revealed an incidence of 2.7% of AF in a cohort of patients with acute coronary syndromes from six adjacent Arabian Gulf countries (Bahrain, Saudi Arabia, Qatar, Oman, United Arab Emirates, and Yemen) collected over 9 months.

Increased age was actually the only predictor of AF in the current study. Considering that the mean age of AMI cohort was 53 years, which is much lower than that in other registries and AMI studies, this may be the reason behind the very low rates of AF in our study. The findings confirm previous reports in other ethnicities that advancing age is the major independent predictor of AF in AMI patients.[4446]

Finally, the study demonstrated a significant impact of AF on survival in patients with AMI with increased in-hospital mortality and stroke rates.

AF has been reported to complicate the course of acute myocardial infarction (AMI) in about 6–21% of hospitalized patients.[4748] There is increasing evidence that there are variations in the susceptibility and incidence of AF complicating AMI in different ethnicities.[4549] However, most of the available literature is derived from trials and studies performed in North America and Europe while other parts of the world are under-represented in AF research.

Herein, the study reports the incidence, predictors of AF after AMI and prognostic implications of this arrhythmia on in-hospital AMI outcomes in two ethnicities that have not been adequately studied together previously (Middle Eastern Arabs and South Asians), in a Middle Eastern country over a 20-years period. Retrospective analysis of a prospective registry of all patients hospitalized with AMI in the State of Qatar from 1991 through 2010 was made. Clinical characteristics and outcomes of AMI patients with and without AF were compared. Sub-analysis according to ethnicity was also performed.

Impact of Religious Fasting on the Burden of Atrial Fibrillation: A Population-Based Study

Salam AM, AlBinali HA, Salim I, Singh R, Asaad N, Al-Qahtani A, Al Suwaidi J. Int J Cardiol 2013 Oct 3;168 (3):3042-3. doi: 10.1016/j.ijcard. 2013.04.131. PubMed PMID: 23642825.

Overall, 1718 Qatari patients were hospitalized for AF during the 20-year period with a mean age of 61. The number of hospitalization for AF was not significantly different in Ramadan (143 cases) when compared to a month before Ramadan (136 cases) and a month after Ramadan (151 cases); P = 0.95. The rate of hospitalizations of patients with underlying myocardial ischemia was significantly lower in Ramadan (9.8%) compared to other months (19.1% and 23.2%; P = 0.02).

This population-based study demonstrated for the first time that fasting has neutral overall effects on AF hospitalizations and suggested a favorable protective effect from fasting on ischemic AF. The same authors have previously studied other cardiovascular disorders in relation to fasting[505152] including; acute coronary syndromes, heart failure and chronic ischemic heart disease. The current study complements these studies and addresses AF that was not previously studied.

There are two hypotheses for the reduction of ischemic AF burden during fasting. The first is that the favorable effects on lipid profile which we reported[53] during fasting provided protection from myocardial ischemia. The other hypothesis is related to the favorable effect of catecholamine inhibition that occurs during fasting. Hunger has been associated with catecholamine inhibition (catecholamine surge has been implicated as a trigger for acute coronary syndromes) and reduced venous return, causing a decrease in the sympathetic tone, which leads to a fall in blood pressure, heart rate and cardiac output.[5455]

Religious fasting is practiced by over one billion Muslims worldwide and represents a radical change in lifestyle for the period of one lunar month (Ramadan).[49] How such prolonged fasting affects the burden of AF is unknown. The objective in this study was to investigate whether Ramadan fasting had any effect on the number of hospitalization with AF in a geographically-defined population.

This study focused only on Middle Eastern (Qatari) patients rather than South Asians (expatriates) because it is a stable population and avoids the bias in the fluctuation of expatriate population in the country that varies from time to time. In addition, more than 95% of Qatari adults fast without fail during the month of Ramadan. All Qatari patients hospitalized with AF in Qatar from 1991 through 2010 were identified. Patients were divided according to the time of presentation in relation to the month of Ramadan; 1 month before, during and 1 month after Ramadan. The number of AF hospitalizations, clinical characteristics and outcome were analyzed in various time periods. We have used hospitalizations for AF as a reflection of AF incidence during the period of study.

Limitation of the study

Studies were constrained by the limitations inherent in all studies of historical, observational design. Inaccuracies in the diagnosis and coding of AF in routine data are well recognized. Temporal changes in referral and coding practices, in diagnostic accuracy, and in awareness of AF as a diagnostic entity may have influenced findings. Other limitations could include missing data or measurement errors, possible confounding by variables not controlled for, as these were observational studies. In addition, the studies focused on in-hospital outcome and long-term data is not available.

CONCLUSIONS

Despite any limitations these studies shed light upon important aspects of AF presentations and outcomes in Middle Eastern Arab and South Asian ethnicities. In the process, several novel observations were reported and new questions were raised that warrant further investigations and further studies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.