Risk for Incident Heart Failure in Atrial Fibrillation

Study Questions:

What are the modifiable risk factors and what is the impact of risk factor modification on heart failure (HF) risk in women with new-onset atrial fibrillation (AF)?

Methods:

The study cohort was comprised of 39,876 female health care professionals in the United States enrolled in the WHS (Women’s Health Study) a large, longitudinal cohort of women without prevalent cardiovascular disease at baseline—to examine the population risk, prognostic implications, and risk factors for incident HF in women with new-onset AF. The final cohort was comprised of 34,736 participants who were free of prevalent cardiovascular disease at baseline. The study authors utilized Cox models incorporating time-varying HF risk factors limited to the subpopulation of women with new-onset AF and without prevalent HF (n = 1,495) to identify significant modifiable risk factors for incident HF.

Results:

In 34,736 women who were free of prevalent cardiovascular disease at baseline, 1,534 women developed new-onset AF (4.4% of the study cohort) and 687 developed HF (2.0% of the study cohort) over a median follow-up of 20.6 (interquartile range [IQR], 19.6-21.1) years. Among 1,534 women with new-onset AF, there were 226 HF events, the majority of which occurred after AF diagnosis (n = 187; 82.7%). Excluding women with HF before AF (n = 39), 1,495 women developed AF without prevalent HF. Of women with new-onset AF and with available echocardiography at the time of AF diagnosis (n = 1,064), only a minority demonstrated structural heart disease, as reflected by the presence of left ventricular hypertrophy (n = 419; 39%), mitral regurgitation (n = 157; 15%), or left atrial enlargement (n = 493; 46%). In multivariable models, new-onset AF was associated with an increased risk of HF (hazard ratio [HR], 9.03; 95% confidence interval [CI], 7.52-10.85). Once women with AF developed HF, all-cause (HR, 1.83; 95% CI, 1.37-2.45) and cardiovascular mortality (HR, 2.87; 95% CI, 1.70-4.85) increased. After taking into account population-level risk factors for mortality and morbidity, the study authors estimated that 9.9% (95% CI, 2.2%-18.3%) of all deaths and 18.2% (95% CI, 1%-35%) of cardiovascular deaths in women with new-onset AF could be attributed to incident HF. In time-updated, multivariable models accounting for changes in risk factors after AF diagnosis, systolic blood pressure >120 mm Hg, body mass index ≥30 kg/m2, current tobacco use, and diabetes mellitus were each associated with incident HF. The combination of these four modifiable risk factors accounted for an estimated 62% (95% CI, 23%-83%) of the population-attributable risk of HF. Compared with women with 3 or 4 risk factors, those who maintained or achieved optimal risk factor control had a progressive decreased risk of HF (HR for two risk factors, 0.60; 95% CI, 0.37-0.95; one risk factor, 0.40; 95% CI, 0.25-0.63; and 0 risk factors, 0.14; 95% CI, 0.07-0.29).

Conclusions:

The authors concluded that in women with new-onset AF, modifiable risk factors including obesity, hypertension, smoking, and diabetes accounted for the majority of the population risk of HF.

Perspective:

This is an important study because it provides data from a large cohort of participants in the WHS. The findings of this study should be kept in mind when designing therapeutic trials for HF. Also, it would be interesting to know whether sleep apnea is an important risk factor in this cohort.

Keywords: Arrhythmias, Cardiac, Atrial Fibrillation, Diabetes Mellitus, Echocardiography, Geriatrics, Heart Failure, Hypertension, Hypertrophy, Mitral Valve Insufficiency, Obesity, Primary Prevention, Risk Factors, Smoking, Women


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