Heart Failure Patients and Implications of Obesity: A Single-Center Retrospective Study

Background and objective The prevalence of heart failure (HF) is on the rise; currently, it affects around five million people in the United States (US) and the prevalence is expected to rise from 2.42% in 2012 to 2.97% in 2030. HF is a leading cause of hospitalizations and readmissions, accounting for a major economic burden to the US healthcare system. Obesity is a widely accepted risk factor of HF; however, data regarding its independent association with HF mortality and morbidity is heterogeneous. Globally, more than two-thirds of deaths attributable to high body mass index (BMI) are due to cardiovascular diseases (CVD). This study aimed to investigate the potential role of obesity (BMI >30 Kg/m2) in HF patients in terms of 30-day readmissions, in-hospital mortality, and the use of noninvasive positive pressure ventilation (NIPPV). Methods In this single-center, retrospective study, all adult (age: >18 years) patients who were hospitalized with a primary diagnosis of HF at the Abington Jefferson Hospital from January 2015 to January 2018 were included. Demographic characteristics were collected manually from electronic medical records. Outcomes were 30-day readmission due to HF, all-cause in-hospital mortality, and requirement for NIPPV. Multivariable logistic regression analysis was conducted to investigate the association of obesity with HF outcomes. Results A total of 1,000 patients were initially studied, of these 800 patients were included in the final analysis based on the inclusion criteria. Obese patients showed higher odds for 30-day readmissions and the use of NIPPV compared to non-obese patients. There was no significant difference in in-hospital mortality in obese vs. non-obese patients. Conclusions Based on our findings, BMI >30 Kg/m2 is an independent risk factor for HF readmissions. Additionally, our results highlight the importance of guidelines-directed medical therapy (GDMT) for HF exacerbation, a low threshold for use of NIPPV in obese patients, promotion of lifestyle modifications including weight loss, and early follow-up after discharge to prevent HF readmissions in the obese population.


Introduction
Heart failure (HF) is a major global health issue, and it results in frequent hospitalizations and high mortality rates. The prevalence of HF has been increasing; currently, it affects around five million people in the United States (US) and the prevalence is expected to rise from 2.42% in 2012 to 2.97% in 2030. In the next decade, the overall prevalence of HF is projected to increase by 23%, with an estimated eight million cases by 2030 [1][2]. HF is the leading cause of hospitalization, with the three-month readmission rate for this group reaching as high as 35%. Although some progress has been made over the past five years in this regard, more than 20% of patients are still readmitted within 30 days and up to 50% by six months [3]. Obesity is a widely accepted risk factor for HF; however, data is heterogeneous regarding its independent association with HF acute severity outcomes [in-patient mortality, readmission, and utilization of noninvasive positive pressure ventilation (NIPPV)]. Globally, more than two-thirds of deaths attributable to   1  2  2, 3  4  5  6   7  8  2  9 high BMI are due to cardiovascular diseases (CVD). Obesity, diabetes, and hypertension (metabolic syndrome) are prevalent in the HF population and contribute to the pathophysiology of congestive HF (CHF) with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Morbid obesity [body mass index (BMI) ≥40.0 kg/m²] is a risk factor for patients with CHF and contributes to an increased risk of readmissions among HF patients. HF and obesity are increasingly prevalent and associated with high morbidity, mortality, and healthcare costs worldwide [4][5]. This study aimed to investigate the potential role of obesity in HF patients in terms of 30-day readmissions, in-hospital mortality, and the use of NIPPV.

Study design
This was a single-center, retrospective study involving all adult (age: >18 years) patients who were hospitalized with a primary diagnosis of HF at the Abington Jefferson Hospital from January 1, 2015, to January 2018. Inclusion and exclusion criteria are mentioned in Table 1. Demographic characteristics were collected manually from electronic medical records. Continuous variables were presented as the mean, and categorical variables were expressed as percentages. Outcomes were 30-day readmission due to HF, inhospital mortality, and requirement for NIPPV. Data collection was focused on determining the rate of HF readmissions, in-hospital mortality due to any cause, and the use of noninvasive ventilation in patients over 18 years of age with HF. HF cases were identified based on the illness at the time of presentation. The data collected from medical records included history/physical examination, demographic variables, as well as EKG and echocardiographic findings. Echocardiograms (2D-transthoracic) were performed by trained technicians and examined by a senior cardiologist to document the ejection fraction (EF). Statistical analysis was performed using SPSS Statistics (IBM, Armonk, NY). Categorical data were analyzed using Pearson's chisquared test, and a p-value of <0.05 was considered statistically significant. Multivariable logistic regression analysis (including age, gender, race, and comorbidities as mentioned in Table 6) was conducted to investigate the association of obesity with HF outcomes. We divided our patients into two major cohorts: Hospitalized patients with a primary diagnosis of HF on left ventricular assist device (LVAD), outpatient milrinone infusions, and cardiogenic shock patients were excluded from the study. All data were recorded in a de-identified manner to maintain confidentiality. All patients were treated at the same institution with optimal guidelines-directed medical therapy (GDMT).

Inclusion criteria Exclusion criteria
All patients who were admitted with heart failure exacerbation from 2015 to 2018 LVAD patients

Discussion
Obesity increases the CVD burden by various physiological mechanisms. It increases insulin resistance, hyperlipidemia, obesity-induced hypertension, development of systemic inflammation, obstructive sleep apnea (OSA), and eventually congestive failure. BMI is a valid and acceptable tool to quantify the severity of obesity; however, it does not account for the content of body or abdominal fat. Regardless, higher BMI has been associated with CVD and poor outcomes [6]. Studies have suggested an inverse relationship between obesity and mortality due to HF. This concept is called the obesity paradox, which refers to lower mortality in obese HF patients than patients who have normal or higher BMI [7]. Our data indicate that obesity is associated with poor outcomes in hospitalized patients with HF. Frequent hospitalization from HF adds to the already strained healthcare provision system in the US. In this study, we noticed an increased 30day readmission rate in obese patients (BMI >30 kg/m 2 ) with a higher incidence of positive pressure ventilation use and increased length of stay (LOS; five days vs. three days) compared to non-obese patients.
We noticed no statistically significant difference in terms of in-hospital mortality in our study though other studies have reported a paradoxical relation of obesity with in-hospital mortality [6][7]. Studies have suggested that HF patients with morbid obesity (>40 Kg/m 2 ) also have a higher mortality rate [8]. It is reasonable to assume that in-patient mortality in our study is underpowered.
Obesity is a potentially expanding public health issue and contributes to high morbidity and mortality. Obesity or increased BMI is associated with increased risk and severity of HF [9]. Increased BMI is considered a risk factor for other CVD including hypertension, diabetes, and hyperlipidemia, and all of these increase the risk of myocardial infarction, which in turn augments the risk of HF [10][11]. Elevated BMI is associated with left ventricular remodeling, and the activation of the renin-angiotensin-aldosterone axis increases sympathetic drive and inflammation [12][13][14][15]. Studies have indicated that NIPPV methods, continuous positive airway pressure (CPAP), and bilevel positive airway pressure (BiPAP) can effectively treat CHF exacerbations. This supports our finding that obese patients were more likely to receive NIPPV compared to non-obese patients. A significant decline in HF hospitalization is observed in patients after bariatric surgery [16][17]. A grade associated between increasing weight loss and HF reduction has been observed secondary to improvement in diabetes, hypertriglyceridemia, and hypertension. We suggest the continuation of GDMT for HF exacerbation, a low threshold for the use of NIPPV in obese patients, promotion of lifestyle modifications including weight loss, and early follow-up after discharge to prevent HF readmissions in the obese population.
Our study has several limitations, including the fact that it was a single-center study, its retrospective study design, and lack of outpatient follow-up. It is plausible that the stratification of HF into HFrEF and HFpEF may produce different results. Future studies are warranted to further the investigation into obesity by stratifying the etiology of HF and its implications in the HF population.

Conclusions
Our study suggests that BMI >30 Kg/m 2 is an independent risk factor for HF readmissions. Furthermore, this data underscores the importance of GDMT for HF exacerbation, a low threshold for the use of NIPPV in obese patients, promotion of lifestyle modifications including weight loss, and early follow-up after discharge to prevent HF readmissions in the obese population.