Faris Al-Khalili

Mass Screening for Untreated Atrial Fibrillation The STROKESTOP Study

Background— The aims of the present study were to define the prevalence of untreated atrial fibrillation (AF) in a systematic screening program using intermittent ECG recordings among 75- to 76-year-old individuals and to study the feasibility of initiating protective oral anticoagulant (OAC) treatment. Methods and Results— Half of the 75- to 76-year-old population in 2 Swedish regions were invited to a screening program for AF. Participants without a previous diagnosis of AF underwent intermittent ECG recordings over 2 weeks. If AF was detected, participants were offered OAC. During the 28-month inclusion period, 13 331 inhabitants were invited. Of these, 7173 (53.8%) participated. Of the participants, 218 (3.0%; 95% confidence interval [CI], 2.7–3.5) were found to have previously unknown AF, and of these, AF was found in 37 (0.5% of the screened population) on their first ECG. The use of intermittent ECGs increased new AF detection 4-fold. A previous diagnosis of AF was known in 9.3% (n=666; 95% CI, 8.6–10.0). Total AF prevalence in the screened population was 12.3%. Of participants with known AF, 149 (2.1%; 95% CI, 1.8–2.4) had no OAC treatment. In total, 5.1% (95% CI, 4.6–5.7) of the screened population had untreated AF; screening resulted in initiation of OAC treatment in 3.7% (95% CI, 3.3–4.2) of the screened population. More than 90% of the participants with previously undiagnosed AF accepted initiation of OAC treatment. Conclusions— Mass screening for AF in a 75- to 76-year-old population identifies a significant proportion of participants with untreated AF. Initiation of stroke prophylactic treatment was highly successful in individuals with newly diagnosed AF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01593553.

Effect of conjugated estrogen on peripheral flow-mediated vasodilation in postmenopausal women

Estrogen replacement protects against cardiovascular morbidity and mortality in postmenopausal women. Conjugated estrogen is the main hormone used in these studies. However, the vascular effects of this type of estrogen are, to a large extent, unexplored. The objective of this study was to evaluate short-term endothelium-dependent vascular effects of intravenously conjugated estrogen at 2 dose levels. Eleven postmenopausal women were included. Each study subject was given 2.5 and 5 mg of conjugated estrogen or placebo in random order with at least 1 week between each investigation in a double-blind study design. The vascular reactivity of the brachial artery was studied using the duplex technique before and 30 minutes after the intravenous administration of study drug. Reactive hyperemia was used to study the flow-mediated vasodilation. Serum estradiol increased significantly and dose dependently 5 minutes after conjugated estrogen infusion. The flow-mediated vasodilation at baseline before drug administration was 1.8 +/- 2.0% (mean +/- SD) after an average 400% increase in local blood flow. Conjugated estrogen at a dose of 2.5 mg caused an increase in flow-mediated vasodilation from 1.8 +/- 2.1% at baseline to 5.4 +/- 2.8% after infusion (p <0.05 vs placebo), whereas 5 mg caused an increase from 1.9 +/- 1.5% at baseline to 7.0 +/- 3.3% after infusion (p <0.05 vs placebo). Intravenous injection of conjugated estrogen significantly improves the peripheral vascular reactivity in postmenopausal women.

Cost-effectiveness of mass screening for untreated atrial fibrillation using intermittent ECG recording

AIMS The aim of this study was to estimate the cost-effectiveness of 2 weeks of intermittent screening for asymptomatic atrial fibrillation (AF) in 75/76-year-old individuals. METHODS AND RESULTS The cost-effectiveness analysis of screening in 75-year-old individuals was based on a lifelong decision analytic Markov model. In this model, 1000 hypothetical individuals, who matched the population of the STROKESTOP study, were simulated. The population was analysed for different parameters such as prevalence, AF status, treatment with oral anticoagulation, stroke risk, utility, and costs. In the base-case scenario, screening of 1000 individuals resulted in 263 fewer patient-years with undetected AF. This implies eight fewer strokes, 11 more life-years, and 12 more quality-adjusted life years (QALYs) per 1000 screened individuals. The screening implies an incremental cost of €50 012, resulting in a cost of €4313 per gained QALY and €6583 per avoided stroke. CONCLUSIONS With the use of a decision analytic simulation model, it has been shown that screening for asymptomatic AF in 75/76-year-old individuals is cost-effective.

Physical activity and exercise performance predict long‐term prognosis in middle‐aged women surviving acute coronary syndrome

Aim.  To evaluate the importance of exercise testing (ET) parameters and leisure time physical activity in predicting long‐term prognosis in middle‐aged women hospitalized for acute coronary syndrome (ACS).

The safety and persistence of non-vitamin-K-antagonist oral anticoagulants in atrial fibrillation patients treated in a well structured atrial fibrillation clinic

Abstract Aims To examine the long-term persistence and safety of the non-vitamin-K-antagonist oral anticoagulants (NOACs) dabigatran (D), rivaroxaban (R) and apixaban (A) in patients with non-valvular atrial fibrillation (AF) treated in the framework of a well structured, nurse-based AF unit for initiation and follow-up of NOAC. Methods Retrospective clinical data were collected for 766 consequent patients from a single cardiology outpatient clinic incorporating the AF unit. Results The follow-up time, median (q1-q3), was 367 days (183–493) for D patients (n = 233), 432 days (255–546) for R patients (n = 282) and 348 days (267–419) for A patients (n = 251). No significant differences were found between the three groups with regard to age, sex, renal function, or CHA2DS2-VASc score. For all bleeding events the incidence rates per 100 patient-years of follow-up (95% confidence interval [CI], p-value) were reported more often for treatment with R (17.2, 12.7–22.8) than for D (7.0, 4.0–11.3, p = 0.001) and A (8.7, 5.2–13.6, p = 0.013). The differences remained significant after adjustment for clinically relevant variables. Discontinuation rates (n = 167) were lower for A (11.5, 7.5–16.8) than for D (30, 23.4–37.9, p < 0.001) and R (23.9, 18.6–30.1, p = 0.001), and were mainly attributed to drug-specific side effects and bleedings. The majority of discontinued patients (n = 142, 85%) proceeded with other types of oral anticoagulants. Limitation The main limitation of the study is the small patient population with a short follow-up time. Conclusion In a retrospective study at a single AF clinic, NOACs showed significantly different bleeding rates and varied discontinuation rates when compared to each other, related mainly to agent-specific side effects and bleedings. The majority of patients that discontinued proceeded with other types of oral anticoagulant.

Significant predictors of poor prognosis in women aged </=65 years hospitalized for an acute coronary event.

Abstract.  Al‐Khalili F, Svane B, Janszky I, Rydén L, Orth‐Gomér K, Schenck‐Gustafsson K (Karolinska Hospital and Karolinska Institutet, Stockholm, Sweden). Significant predictors of poor prognosis in women aged ≤65 years hospitalized for an acute coronary event. J Intern Med 2002; 252: 561–569.

Prognostic Value of Exercise Testing in Women After Acute Coronary Syndromes (The Stockholm Female Coronary Risk Study)

Exercise electrocardiographic testing is a widely used noninvasive procedure for the diagnostic and prognostic assessment of coronary heart disease. However, compared with men, the prognostic value of exercise testing is uncertain in women due to limited number of women included in studies. Early adequate risk stratification in female patients recovering from acute coronary syndrome is becoming more important as newly published studies show a high mortality rate in young female patients with myocardial infarction compared with men at the same age, 1 and that coronary intervention studies show uncertain effects in women with unstable coronary syndrome. 2 In the Stockholm Female Coronary Risk Study we had the opportunity to address this issue in a cohort of women #65 years old who had been hospitalized for acute coronary syndromes in the greater Stockholm area. This study describes the value of exercise testing parameters for the prediction of recurrent coronary events during a 5-year follow-up period. ••• The Stockholm Female Coronary Risk Study, a community-based study, included women #65 years old, residing in the greater Stockholm area, and hospitalized for an acute coronary event in 1 of the 10 coronary care units in Stockholm, between February 1991 and February 1994. Patients were included if their hospital records indicated acute myocardial infarction (AMI) or unstable angina pectoris (UAP). Full details of the study have been previously published.3‐5 Clinical screening, including exercise testing, was performed 3 to 6 months after the index event. During the recruitment period, 335 consecutive women were identified. Forty-three of these patients (13%) could not be included due to death before the examination (n 5 5), severe concomitant illness (n 5 3), transportation difficulties (n 5 2), and other nonmedical reasons (n 5 20). The present study cohort consisted of 292 patients. Exercise testing could not be performed in 19 of the patients (7%) for various medical reasons (mainly orthopedic or neurologic disabilities).

Intracoronary ultrasound measurements in women with myocardial infarction without significant coronary lesions.

Methods Morphologic characteristics of coronary arteries in eight women with myocardial infarction and angiographically normal or not significantly stenosed vessels were investigated with intracoronary ultrasound. The infarct-related vessel was assessed by three-dimensional volumetric analysis and compared with a control vessel from a noninfarcted area. Results Atherosclerosis was found in all infarct-related arteries. The plaques were predominantly soft, eccentric, poorly calcified, and with little lipid pools or none at all. Although the average area and thickness of plaques and cross-sectional narrowing of the infarct-related arteries were greater than those of control arteries, there were no patognomonic characteristics of plaques in the infarct-related vessels. Conclusion The possibility that atherosclerosis is the main etiologic factor for myocardial infarction can not be excluded even for women without an angiographically obvious coronary stenosis in the infarct-related vessels.

The effects of exercise capacity and sedentary lifestyle on haemostasis among middle-aged women with coronary heart disease.

Previous studies have established a link/relationship between haemostatic factors and increased risk of cardiovascular disease. In addition,physical conditioning is associated with lower coronary heart disease risk.The purpose of this study was to assess the association between physical exercise and haemostatic factors among middle-aged women surviving an acute coronary event.The Stockholm Female Coronary Risk Study included 292 women aged < 65 years, resident in the greater Stockholm area, who were hospitalized for an acute coronary syndrome. Extensive clinical screening including exercise testing, and blood tests were performed 3–6 months after the coronary event. Self-reported physical activity was assessed by a WHO questionnaire. Patients on warfarin treatment were excluded from our analyses. Haemostatic factors were generally higher among physically inactive patients when compared to physically active women in our univariate models. Exercise capacity had a statistically significant relationship with factor VII antigen (p=0.039) and vWFag (p=0.038) even in our multiadjusted analyses. Physical inactivity and poor physical fitness are associated with a potentially prothrombotic blood profile in middle aged women with coronary heart disease.

Safe automatic one-lead electrocardiogram analysis in screening for atrial fibrillation

Aims Screening for atrial fibrillation (AF) using intermittent electrocardiogram (ECG) recordings can identify individuals at risk of AF-related morbidity in particular stroke. We aimed to validate the performance of an AF screening algorithm compared with manual ECG analysis by specially trained nurses and physicians (gold standard) in 30 s intermittent one-lead ECG recordings. Methods and results The STROKESTOP study is a mass-screening study for AF using intermittent ECG recordings. All individuals in the study without known AF registered a 30-s ECG recording in Lead I two times daily for 2 weeks, and all ECGs were manually interpreted. A computerized algorithm was used to analyse 80 149 ECG recordings in 3209 individuals. The computerized algorithm annotated 87.1% (n = 69 789) of the recordings as sinus rhythm/minor rhythm disturbances. The manual interpretation (gold standard) was that 69 758 ECGs were normal, making the negative predictive value of the algorithm 99.9%. The number of ECGs requiring manual interpretation in order to find one pathological ECG was reduced from 288 to 35. Atrial fibrillation was diagnosed in 84 patients by manual interpretation, in all of whom the algorithm indicated pathology. On an ECG level, 278 ECGs were manually interpreted as AF, and of these the algorithm annotated 272 ECGs as pathological (sensitivity 97.8%). Conclusion Automatic ECG screening using a computerized algorithm safely identifies normal ECGs in Lead I and reduces the need for manual evaluation of individual ECGs with >85% with 100% sensitivity on an individual basis.