Atrial Fibrillation Registry for Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study.
Condition: Atrial Fibrillation; Peripheral Vascular Disease
MeSH terms: Atrial Fibrillation; Vascular Diseases; Peripheral Vascular Diseases; Peripheral Arterial Disease
Study type: Observational

Summary: 
      Atrial fibrillation (AF) is the most common sustained dysrhythmia encountered in clinical
      practice in North America and Europe, accounting for approximately one-third of all
      hospitalizations for a cardiac rhythm abnormality. The presence of AF markedly increases the
      patient's risk for developing arterial embolism and stroke, depending on the presence of
      other clinical conditions, such as hypertension and diabetes. AF is associated with a
      fivefold increased risk for stroke, and is estimated to cause 15% of all strokes.

      Patients with AF frequently have several risk factors for atherosclerosis, including
      hypertension, diabetes, and dyslipidemia. Accordingly, systemic signs of atherosclerosis can
      be detected in AF patients, and these likely accounts for an enhanced risk of coronary heart
      disease. In addition to cerebrovascular disease, patients with AF may suffer from coronary
      events including myocardial infarction (MI), but the rate of MI in AF patients seems to be
      variable, but often underestimated.

      Moreover, coexistence of peripheral arterial disease (PAD) is a relevant clinical sign of
      systemic atherosclerosis.

      Ankle-brachial index (ABI) is a simple, inexpensive, and non-invasive PAD measurement, even
      at the pre-symptomatic phase when intervention can improve prognosis and prevent or delay
      severe complications ABI is calculated by measuring the systolic blood pressure in the
      posterior tibial and/or the dorsalis pedis arteries either in both legs or 1 leg chosen at
      random (using a Doppler probe or alternative pulse sensor), with the lowest ankle pressure
      then divided by the brachial systolic blood pressure. In addition to peripheral artery
      disease, the ABI also is an indicator of generalized atherosclerosis because lower levels
      have been associated with higher rates of concomitant coronary and cerebrovascular disease,
      and with the presence of cardiovascular risk factors.

      Two large studies in patients with AF document the existence of PAD in about 3-5% of
      patients. It is possible, however, that such an incidence has been underestimated as only
      symptomatic patients were considered as affected by PAD. As PAD is an important marker of
      systemic atherosclerosis, its association with AF reinforces the concept that patients with
      AF have systemic atherosclerosis that potentially account for coronary complications.

      To date, a national registry of AF patients is not available to verify the real impact of
      cardiovascular events in this clinical setting.
    

Detailed description: 
      Study design: Prospective longitudinal study

      Methods and Materials: The investigators planned to assess at baseline and at scheduled
      follow up visits :

        1. Ankle-Brachial Index measurement

        2. Anamnestic clinical information and Anthropometric measurements

        3. Echocardiogram (volume size), electrocardiogram (AF type)

        4. Outcome events such as nonfatal or fatal acute myocardial infarction, target lesion or
           vessel revascularization nonfatal or fatal ischemic stroke, transient ischemic attack,
           death from any cardiac or vascular cause, death from any cause Study duration: 3 years
           follow-up Statistical methods: The prevalence will be calculated by exact confidence
           intervals (Wilson method). The cumulative incidence will be calculated by the
           product-limit estimator of Kaplan-Meyer and presented with confidence intervals at 95%.
           The incidences and prevalences will be then adjusted through appropriate multivariate
           analysis (using the Cox proportional hazards model and logistic model) that will take
           into account the effect of potential confounders. Similarly, the effect-center presence
           will be checked and possibly removed. Secondary endpoints will be assessed by using
           Log-rank test method, and by the Cox model (with time-dependent effects) multivariate
           analysis.

      Subgroups analysis will be also conducted for patients with first onset of AF or recurrent AF
      Sample size: The investigators plan to include in the study n = 3,000 AF patients, with
      competitive recruitment between centers involved in the study. The sample size was calculated
      assuming an expected prevalence of 19% at time zero, and in order to obtain a confidence
      interval 95% to prevail at time zero whose distance from the edge is less than or equal to
      1.4%. This sample size yields a power greater than 99.9% for the secondary endpoint, assuming
      an event rate of 19% for patients with ABI <=0.9, and 10% for patients with ABI >0.9.An
      interim analysis showed an ABI prevalence, calculated by exact confidence intervals, of 21%
      in patients with AF, it is considered to interrupt the enrollment, as the observed prevalence
      is greater than two percentage points higher than that assumed. The sample size is amended as
      follows: a sample of 2027 patients leads to the expected prevalence of 21% with a confidence
      interval width of 3.5. This sample size has no impact on the power of the secondary
      objective.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        The investigators plan to include in the study n = 3,000 AF patients, with competitive
        recruitment between centers involved in the study. The sample size was calculated assuming
        an expected prevalence of 19% at time zero, and in order to obtain a confidence interval
        95% to prevail at time zero whose distance from the edge is less than or equal to 1.4%.
        This sample size yields a power greater than 99.9% for the secondary endpoint, assuming an
        event rate of 19% for patients with ABI <=0.9, and 10% for patients with ABI >0.9.An
        interim analysis showed an ABI prevalence, calculated by exact confidence intervals, of 21%
        in patients with AF, it is considered to interrupt the enrollment, as the observed
        prevalence is greater than two percentage points higher than that assumed. The sample size
        is amended as follows: a sample of 2,027 patients leads to the expected prevalence of 21%
        with a confidence interval width of 3.5. This sample size has no impact on the power of the
        secondary objective.
      
Keywords: Atrial Fibrillation; ABI; PAD; Registry; Italian