Clinical trends in atrial fibrillation at the turn of the millenium

Atrial fibrillation (AF) is a highly prevalent sustained dysrhythmia. AF has been estimated to currently affect over 6 million patients in Europe and approximately 3.5 million in the United States, and this number continues to grow rapidly because of the increasing proportion of the ageing population with underlying heart disease. Reports from the Cardiovascular Health Study and the Framingham study indicate that the incidence of AF in subjects under 64 years is 3.1 cases in men and 1.9 cases in women per 1000 person-years, rising sharply to about 19.2 per 1000 person-years in those 65–74 years, and is as high as 31.4–38.0 in octogenarians (Fig. 1) [1, 2]. Incidence of atrial fibrillation in the Göteborg study and in three population – based studies: the Framingham Heart Study, the Cardiovascular Health Study, and the Manitoba Follow-up Study. The values are plotted at the midpoint of the age range. Atrial fibrillation constitutes a major public health problem because it is associated with a considerable risk for mortality and morbidity, largely because of stroke, and it leads to more hospital admissions than any other dysrhythmia [3–5]. In addition to often disabling symptoms and impaired quality of life, AF can precipitate heart failure and trigger potentially fatal ventricular dysrhythmias. Reflecting this worldwide ‘epidemic’ of AF, data from the US, Scottish and Danish studies reported a 2–2.5-fold increase in hospitalization rates for AF between 1982–1986 and 1992–1996 [6–8]. Newer pharmacological and nonpharmacological therapies are rapidly being developed, suggesting that no one single strategy has accomplished the task of treating AF safely and efficiently. This relative lack of success in treatment and prevention of this dysrhythmia which has been known for over 100 years, may be because of our incomplete present knowledge of its pathophysiology and risk factors which precipitate its occurrence. The Framingham study, initiated in 1948, identified several independent risk factors for AF which have mostly been confirmed in many other population surveys (Table 1). Many of these risk factors are heart diseases themselves, such as hypertension and myocardial infarction. The primary pathologies underlying or promoting the occurrence of AF vary, probably, more than for any other concomitant cardiac abnormality, ranging from cardiac autonomic imbalance through organic heart disease to metabolic disorders, such as diabetes mellitus and hyperthyroidism. A cause-to-effect relation is often cannot be established, suggesting the presence of a complex interplay between primary disorders, precipitating factors and AF. For example, AF has been recognized as a major independent risk factor for embolic stroke or transient ishaemic attack, being associated with a 4–5-fold increased risk than in the unaffected population [4]. However, there is also evidence to suggest that stroke may precipitate the occurrence of AF, perhaps because of haemodynamic and autonomic consequences [9]. Furthermore, hypertension is a powerful independent predictor of stroke in nonrheumatic AF [10, 11] and an important risk factor for AF operating via electrophysiological and structural changes in the heart associated with myocardial hypertrophy, increased impedance to left ventricle and left atrial emptying because of a noncompliant aorta and increased peripheral resistance. Therefore, identification of specific risk factors potent to precipitate AF and the way of their elimination or modification merit special appreciation. In their study published in this issue of Journal of Internal Medicine, Wilhemsen, Rosengren and Lappas have addressed epidemiology and risk factors for AF in 7495 men aged 55 years or older who participated in the Multifactor Primary Prevention Study started in Göteborg in 1970. To place the present study in perspective, it should be mentioned that it was originally an interventional programme aimed at the reduction or modification of risk factors for coronary artery disease, such as smoking, raised cholesterol levels and hypertension [12]. The programme enrolled three groups of men aged 47–55 years: an interventional group and two control groups, about 10 000 subjects each, and was scheduled to run for 10 years. After initial screening for risk factors for coronary heart disease, subjects in the interventional group received antihypertensive treatment, cholesterol-lowering drugs, and an extended active antismoking educational programme. The last risk assessment and examination in 1980–1983 revealed a substantial and comparable decrease in risk factors in the interventional and control groups which, however, did not translate into a reduction in total or cardiovascular mortality, and morbidity. Moreover, in the interventional group, the mortality and morbidity rates were significantly lower in 7495 individuals who actively participated in the programme (the present study is based on the analysis of this subgroup) compared with 2509 noncompliant subjects. For example, there was a striking difference in total mortality after a mean follow-up of 11.8 months: 9.8 vs. 22.3%. Of note, ‘nonparticipants’ were more likely to have a lower socio-economic status and a higher level of alcohol consumption – factors that would favour higher AF rates than those reported. A trend towards reduction in risk factors in a general population could be attributable to improvements in the treatment of hypertension and heart failure, wider use of cholesterol-lowering drugs, ACE inhibitors and β-blockers, and to results of various antismoking and diet-modification educational programmes. As a result, there are changes in the structure of risk factors for AF. Hypertension, one of the most powerful risk factors for AF in the Framingham and other studies, was no longer closely associated with hospitalizations for AF. In the Danish National Hospital Discharge Register, hypertension also was seen in 17–20% of patients with AF, headed by coronary artery disease and congestive heart failure which accounted for about 40 and 30% of AF cases, respectively [8]. However, there can be the selection bias inherent in hospital-based series, resulting in patients with AF who are seen at hospital may have more severe concomitant heart disease than patients identified in population surveys. Assessment of the prevalence of AF in a general population may be inaccurate when using hospital registries leaving many cases of AF in the community unrecognized. However, data from Göteborg researchers suggest that AF may be even more common than was assumed from the previous studies, because the rates of AF estimated using medical records were similar to the rates of dysrhythmia assessed using both medical records and regular, e.g. bi-annual, medical examinations (Fig. 1). Once more the presence of constitutional factors that can predispose to AF, such as an increased body mass index and a higher body height, has been identified. Increased body mass index was reported as a risk factor in the Framingham and the Manitoba Follow-up studies [2, 13]. Of note, height was an independent predictor of AF in the GUSTO I thrombolysis trial involving over 40 000 patients with acute myocardial infarction [14]. Understanding of the relation of these factors to the occurrence of AF is incompletely understood. Metabolic disorders and genetic factors seem to be implicated. Interestingly, the presence of a stroke in mothers was associated with a 1.5-fold risk for the development of AF, suggesting that there may be a genetic predisposition to AF. Indeed, identification of a gene defect linked to chromosome 10q in the Spanish family, nearly half members of which presented with AF, supports the hypothesis of familial AF [15]. The results of this study have confirmed once more that AF remains a substantial global health burden and have highlighted the need for targeted screening to detect individuals who are likely to develop this dysrhythmia. The unacceptable results of antidysrhythmic therapy targeted the electrophysiological substrate for AF and adverse effects on mortality in patients with organic heart disease, now made the therapeutic approach move ‘up-stream’ and focus on treatment of the underlying pathology in order to prevent or delay myocardial changes leading to the formation of the dysrhythmogenic substrate. Many risk factors are consistently shared by AF and other cardiac co-morbidities, and their eradication would theoretically confer a substantial benefit in terms of public health and healthcare burden. The identification and modification of risk factors which do not directly relate to pathological conditions, e.g. constitutional factors, could lead to more effective early diagnosis of the tendency to AF and therefore, make preventative strategies more efficacious. Identification of such factors specific for AF would make possible intervention early in the course of the disease when preventative or corrective strategies are most efficient, or even prior to the occurrence of the underlying disease.

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