Short‐Term Survival in Elderly Patients Hospitalized for Heart Failure: The Role of Diabetes Mellitus and Newly Recognized Hyperglycemia

To the Editor: Heart failure (HF) is a major public health problem, frequently associated with a poor prognosis. In recent years, an array of options has been identified to treat patients with HF. Many of these options, such as implantable defibrillators and biventricular pacemakers, are invasive and expensive procedures, and the extent to which these interventions should be used in elderly patients with HF is unknown, in part because clinically useful markers to predict short-term prognosis are not available.1 In this framework, the predictive role of diabetes mellitus is controversial, and few data describe the importance of newly recognized hyperglycemia.2-6 The factors associated with 3-month mortality, in particular the role of diabetes mellitus and newly recognized hyperglycemia, were studied in a cohort of hospitalized elderly patients with HF. This prospective observational study was conducted on a population of 340 patients with new-onset or worsening HF admitted to the geriatric ward of the Poliambulanza Hospital (Brescia, Italy). The institutional review board approved the study. HF was the primary reason for admission, and diagnosis was made clinically or with echocardiography and confirmed with chest X-ray. Variables collected included demographic information, biological parameters (serum albumin, creatinine, sodium, urea, cholesterol, C-reactive protein, troponin I, plasma hemoglobin, and hematocrit), left ventricular function, systolic blood pressure and heart rate at admission, New York Heart Association class, activities of daily living according to Barthel Index, Acute Physiology Score (APS), cognitive status according to Mini-Mental State Examination (MMSE) score, and Charlson Comorbidity Index, main diagnoses, drugs on admission and at discharge, and length of stay in the hospital. Medications at discharge were angiotensin-converting enzyme inhibitors (82%), angiotensin II receptor blockers (8.1%), beta-blockers (52.3%), loop diuretics (96.0%), and aspirin (95.4%). There were no statistically significant differences between the groups for drug treatment (data not shown). For the aims of the study, the patients were divided into three groups according to their glycemic status (Table 1). Diabetes mellitus was defined as reported history or documented treatment. Fasting serum glucose levels greater than 126 mg/dL in patients without diabetes mellitus was considered to be a newly recognized hyperglycemia. Three-month mortality was 8.2% overall, 5.4% in normal glycemic patients (n=11), 9.9% in those with diabetes mellitus (n=10), and 20% in those with newly recognized hyperglycemia (n=7). Predictors of mortality in the bivariate analysis were age (≥80), APS (>4), S-albumin (<3.5 g/dL), hyponatremia (<135 mmol/L), MMSE score (<18), number of drugs, faster heart rate, and newly recognized hyperglycemia. After controlling for variables that were statistically significant (P<.05) in bivariate analyses, APS greater than 4 (odds ratio (OR)=2.8, 95% confidence interval (CI)=1.1–7.4), MMSE score less than 18 (OR=3.1, 95% CI=1.2–7.8), and newly recognized hyperglycemia (OR=2.7, 95% CI=1.0–9.4) were independent factors associated with 3-month mortality in multivariate logistic regression analysis. These results reveal that diabetes mellitus (29.7%) and newly recognized hyperglycemia (10.3%) are common in this population. These data confirm findings from a previous study6 of a strong relationship between newly recognized hyperglycemia and mortality. Although the underlying mechanisms for the development of hyperglycemia in HF are not fully understood, several have been proposed, among these being neurohormonal adaptations, such as activation of the renin-angiotensin-aldosterone and of the sympathetic nervous system. In addition, HF is often characterized according to the increase of circulating proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin (IL)-6, IL-1-beta, and IL-2.7 Furthermore, the neurohormonal adaptations and the increase of circulating cytokines produce insulin resistance and hyperglycemia. These alterations correlate with the severity of HF and are independent predictors of mortality.7, 8 It is also interesting to speculate whether hyperglycemia in these patients may be an “innocent” marker of HF severity or a modifiable mediator of adverse outcomes. Further study is needed to determine whether optimal treatment of newly recognized hyperglycemia could lead to better outcomes and a reduction in mortality. These results also confirm previous data demonstrating the predictive role of dementia in HF.1, 9 The APS was an independent marker of mortality in this population with HF. Because APS is the sum of 12 variable points reflecting severity of illness, including clinical (e.g., heart rate, respiratory rate) and biochemical parameters (e.g., serum sodium, creatinine levels),10 it may be inferred that this score is a better predictor of negative outcome than the single variables. In conclusion, in elderly patients with HF, newly recognized hyperglycemia, high APS, and dementia predict short-term mortality. These results may enable clinicians to better advise patients about prognosis, thus individualizing the management of HF, excluding more-aggressive interventions, and allowing considerations for palliative care. Conflict of Interest: Intissar Sleiman, Renzo Rozzini, Alessandro Giordano, and Marco Trabucchi had no financial support for research, are not consultants for any company, and have no company holdings or patents. Author Contributions: Intissar Sleiman, Renzo Rozzini, Alessandro Giordano, and Marco Trabucchi are the coauthors of the letter; they had equal roles in study concept and design, acquisition of subjects and data, analysis and interpretation of data, and preparation of the article. Sponsor's Role: The funding sources had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; or the preparation, review, or approval of the letter.