In this study of 2,416 African American participants from the ARIC cohort, LV systolic dysfunction was associated with an increased rate of hospitalization due to both cardiovascular and non-cardiovascular causes. In fact, the absolute difference in number of hospitalizations related to LV dysfunction was similar for cardiovascular (mean 2.0) and non-cardiovascular (mean 1.7) admissions and nearly half of excess hospitalizations were attributable to non-cardiovascular causes. Risk was independent of an array of potential confounders for both cardiovascular and non-cardiovascular diseases. These results were robust for both the hospitalization rate and time to event analyses and were present among asymptomatic individuals without diagnosed HF.
Previous studies of LV systolic dysfunction and hospitalization risk have yielded mixed results, but they focused exclusively on readmissions among individuals with clinically diagnosed HF. 8–11, 14
Community-wide studies have found an increased risk for cardiovascular hospitalization among individuals with asymptomatic LV systolic dysfunction; 16
however, there exists limited information about the association between LV dysfunction and non-cardiovascular hospitalizations, which accounted for over half of the admissions in our study. For this reason, we quantified the extent to which previous studies may have underestimated the total hospitalization burden associated with LV dysfunction in the community.
We found that LV dysfunction was associated with hospitalizations for a variety of causes, including for pulmonary, gastrointestinal, and kidney diseases. Dunlay and colleagues recently examined the etiology of hospitalizations among heart failure patients in the community and found that non-cardiovascular hospitalizations accounted for substantial morbidity in an older population in Olmsted County, Minnesota. 5
Of note, in that study LV dysfunction was not associated with increased risk of all-cause hospitalizations and the relationship of LV function to etiology of admission was not addressed. To our knowledge, no other studies have examined the reason for hospitalizations among individuals with LV dysfunction.
Participants with LV dysfunction had increased rates of both COPD and pulmonary admissions, a notable clinical finding as individuals with LV dysfunction are frequently admitted for HF which can present in a similar manner to pulmonary diseases. 31, 32
Previous research among Medicare participants with HF have demonstrated high readmission rates for pulmonary diagnoses. 4, 6
Studies have shown that 30% of heart failure patients have concurrent COPD, which is only partially due to common risk factors. Individuals with COPD have systemic inflammation which can lead to coronary disease and LV dysfunction, and both heart failure and COPD lead to muscle atrophy and worsening cardiopulmonary function. 31
Our results of an association between LV dysfunction and COPD morbidity was, therefore, not surprising. Nonetheless, the overall proportion of COPD hospitalizations was small. Furthermore, we had expected to find a relationship between LV dysfunction and pneumonia. We hypothesize that the relatively few number of pulmonary hospitalizations may point to the diagnostic difficulty in differentiating HF, COPD, and pneumonia, with clinicians attributing a greater number of hospitalizations to HF in our study.
LV dysfunction was associated with increased rates of hospitalizations for admissions related to kidney disease and diabetes. Both are risk factors for LV dysfunction and cardiovascular diseases; 33
nevertheless, the results were significant even after adjustments for cardiovascular risk factors including diabetes status and eGFR.
We found LV dysfunction was associated with an increased rate of gastrointestinal admissions. The overlap between gastrointestinal diseases and HF in general has been less well recognized. HF may lead to intestinal ischemia and bowel edema with resulting bacterial and endotoxin translocation. 34
Indeed, gastroenteritis and gastrointestinal hemorrhage have been shown to be common admission diagnoses among HF patients. 4
Our findings further support the association between gastrointestinal morbidity and HF in general.
Among individuals without prevalent HF at baseline, LV dysfunction was associated with an increased risk of total hospitalization, with similar increased rates for cardiovascular (2.84; 95% CI 1.47–5.51) and non-cardiovascular (aIRR 2.41; 95%CI 1.51–3.87) hospitalizations. Previous population studies have demonstrated that asymptomatic left ventricular systolic dysfunction is associated with increased risk of cardiovascular morbidity and mortality. 16, 17
Furthermore, clinical trials have shown that pharmacotherapy reduces cardiovascular events among individuals with asymptomatic LV dysfunction, 12, 35, 36
which has led to discussion about screening in the community. 37–39
Our study found a risk associated with asymptomatic LV dysfunction beyond cardiovascular disease, which implies that early detection may offer benefit to reduce morbidity associated with non-cardiovascular diseases. For instance, given their high incidence rate of pulmonary admissions, individuals with asymptomatic LV dysfunction may be an appropriate group for pneumococcal and influenza vaccinations to prevent hospitalization.
This study has several important strengths. The prospective, longitudinal nature of the study permitted for accurate assessment of hospitalization rates. We were able to follow a large, community-based cohort of middle aged African Americans who are at high risk of HF and often underrepresented in trials. 32
The time of follow up was significant at a median of 10.8 years. Ejection fraction was assessed using a standard protocol with quality control which should have resulted in accurate measurement and classification of the primary exposure.
Several weaknesses of the study deserve mention. First, our study is limited by the small number of individuals found to have LV systolic dysfunction: 2.5% among the entire cohort and 1.7% among individuals without symptomatic heart failure. These prevalences are about half of that observed in other population-based studies that defined LV systolic dysfunction as an ejection fraction of less than 50%. 17, 23, 24, 39
Of note, these previous studies looked at populations that were predominantly white; African Americans are at higher risk of hypertension and left ventricular hypertrophy, which are strongly associated with diastolic dysfunction. 32
Further research should address the differences in risk and prognosis of diastolic versus systolic dysfunction among the African-American population, which we were unable to assess due to significant limitations in echocardiographic evaluation of diastolic dysfunction in the ARIC study. 22
Second, although we used various methods to ensure the accuracy of number of hospitalizations, diagnoses were based on ICD-9 coding which is subject to misclassification. Misclassification could have occurred in the differentiation of pulmonary and cardiac causes of dyspnea, which frequently have similar clinical presentations. Some COPD hospitalizations may have therefore represented HF hospitalizations, and vice versa. This may limit the inferences from cause specific hospitalization data but strengthens the rationale for looking at all hospitalizations regardless of cause. Third, due to study protocol, information related to left ventricular function was categorical and we were unable to analyze ejection fraction as a continuous variable. Fourth, many of the study participants had zero hospital admissions, while some individuals had multiple admissions. This distribution may have skewed the results in the incident rates analyses as some individuals may have had a disproportionate effect on outcomes. However, the distribution of hospitalizations would not have affected the time to event analyses, which produced similar results. As we focused exclusively on African-Americans, a group which may be at increased risk of hospitalizations, 40
our results may not be generalizable to other races or ethnicities.
While we found that LV dysfunction was associated with increased risk of non-cardiovascular hospitalizations, we cannot determine the mechanism of risk. Concurrent increased rates of cardiovascular and non-cardiovascular hospitalizations may be a result of clustering tendencies, common risk factors, pathophysiologic overlap, or another mechanism. Further research will need to address whether measures such as screening for non-cardiovascular diseases or treatment of cardiovascular disease among individuals with LV dysfunction have efficacy in the prevention of non-cardiovascular hospitalizations.
The primary implication of our study is that LV systolic dysfunction confers an underappreciated risk of hospitalization due to non-cardiovascular disease. If additional studies confirm our results, initiatives to reduce hospitalizations should consider the impact of LV dysfunction on a broad array of diseases. Management of individuals with LV dysfunction should focus on prevention and treatment of both cardiovascular and non-cardiovascular comorbidities. Further research should examine a possible mechanism of an effect of left ventricular dysfunction on non-cardiovascular conditions, especially pulmonary and gastrointestinal diseases.