General fatigue, exertional fatigue, and their co-occurrence may be associated with poorer quality of life in older adults with stage B heart failure, while exertional fatigue alone or with general fatigue was associated with a greater risk of incident clinical heart failure over a median follow-up of 8.4 years, according to findings from the Atherosclerosis Risk in Communities study.
Investigators conducted an analysis of 2,972 community-dwelling adults with stage B heart failure who participated in Atherosclerosis Risk in Communities visit 5 between 2011 and 2013. Stage B heart failure was defined as the absence of clinical heart failure with structural heart disease, increased filling pressures, or heart failure risk factors accompanied by elevated cardiac biomarkers. General fatigue was assessed using the five-item Patient-Reported Outcomes Measurement Information System fatigue scale at the first semiannual follow-up after visit 5, while the modified Medical Research Council breathlessness scale, measured at visit 5, was used as a proxy for exertional fatigue. The participants were categorized as having low or no fatigue, high general fatigue only, high exertional fatigue only, or high general and exertional fatigue. Quality of life was measured using the 12-Item Short Form Health Survey. Incident heart failure events were ascertained through surveillance of hospitalizations and mortality followed by expert adjudication through 2020. The investigators used multivariable linear regression in cross-sectional analyses of quality of life, Cox proportional hazards regression in prospective analyses of incident clinical heart failure, and competing-risks regression to assess associations with heart failure phenotypes.
Among the cohort, 71% had low or no general and exertional fatigue, 10% had high general fatigue only, 12% had high exertional fatigue only, and 7% had both high general and exertional fatigue. Compared with those reporting low or no general and exertional fatigue, those in the fatigue groups were more likely to identify as female or Black as well as have lower educational attainment, diabetes, higher body mass index, lower estimated glomerular filtration rate, and greater depressive symptom burden.
All fatigue categories were associated with lower physical quality-of-life scores compared with the low-fatigue group. The participants with both general and exertional fatigue had the largest reductions, with physical quality-of-life scores approximately 11 points lower and mental quality-of-life scores approximately six points lower than those in the reference group. Those with high general fatigue alone and high exertional fatigue alone also had lower physical quality-of-life scores, although the reductions were smaller compared with those observed with co-occurring general and exertional fatigue. The investigators reported similar, but smaller, trends across fatigue categories for mental quality of life.
During a median follow-up of 8.4 years, they documented 338 new clinical heart failure events. Crude incidence rates increased across fatigue categories, from approximately 12 events per 1,000 person-years among those with low or no fatigue to approximately 28 events per 1,000 person-years among those with both general and exertional fatigue. After multivariable adjustment, high exertional fatigue alone was associated with incident clinical heart failure, as was the combination of high general and high exertional fatigue. High general fatigue alone was not independently associated with incident clinical heart failure.
“Our findings build upon prior work by showing that patient‐reported general and exertional fatigue in pre‐[heart failure], and particularly their co‐occurrence, also have important risk implications for the development of clinical [heart failure],” wrote lead study author Noelle V. Pavlovic, PhD, RN, of the Boston College William F. Connell School of Nursing, and colleagues.
Among the 338 incident heart failure events, 173 were heart failure with preserved ejection fraction and 143 were heart failure with reduced ejection fraction. Twenty-two events were undefined. Competing-risks regression showed that all three fatigue categories were independently associated with incident heart failure with preserved ejection fraction, whereas no fatigue category was significantly associated with heart failure with reduced ejection fraction. The highest risk of heart failure with preserved ejection fraction occurred among the participants with both general and exertional fatigue. The results were similar after additional adjustment for physical activity and in sensitivity analyses excluding those with heart failure events within the first 3 years of follow-up, outpatient heart failure diagnoses at or before visit 5, or elevated N-terminal pro–B-type natriuretic peptide concentrations.
The investigators noted that the observational design remained subject to residual confounding and that the breathlessness scale may not have fully captured exertional fatigue. Several potential confounders related to fatigue, including cardiorespiratory fitness, sleep apnea, thyroid disease, cancer, anemia, and lung disease, were not well characterized in the Atherosclerosis Risk in Communities study.
The Atherosclerosis Risk in Communities study received federal funding from the National Heart, Lung, and Blood Institute, part of the National Institutes of Health. Full disclosures of the study authors can be found in the study.
