ABSTRACT
BACKGROUND: Both type 2 diabetes mellitus (T2DM) and frailty are strongly associated with congestive heart failure (CHF). Individuals with T2DM and CHF have a high frailty burden. The association of frailty with HF, all-cause, and cardiovascular mortality in patients with T2DM has not been thoroughly explored. METHODS: This study included 2894 adults with T2DM from the National Health and Nutrition Examination Survey (NHANES) database over ten cycles (1999-2018) and followed up for all-cause and cardiovascular mortality through 31 December 2019. The frailty index (FI) was calculated using a 46-item deficit model to assess frailty status. Weighted multivariable logistic regression was performed to explore the relationship between frailty and CHF in patients with T2DM. Weighted restricted cubic splines were used to evaluate the non-linear relationship between FI and outcome. All-cause mortality and cardiovascular mortality association with FI was assessed using the Kaplan-Meier curve and COX proportional hazards regression accounting for sampling weights. Subgroup and sensitivity analyses were performed to evaluate the robustness of the results. RESULTS: After the adjustment of essential confounders, a higher frailty index in T2DM was associated with increased odds of CHF (odds ratio [OR] for per 1-SD increase, 2.02, 95% confidence interval [CI] 1.67-2.45; P < 0.0001). The presence of frailty T2DM (OR, 3.60; 95% CI 2.34-5.54; P < 0.0001) was associated with a significant increase in the prevalence of CHF compared to non-frailty T2DM in a fully adjusted model. During the median follow-up of 6.75 years, per 1-SD increase in FI was associated with a 41% higher risk of all-cause mortality and a 30% higher risk of cardiovascular mortality after being adjusted for all confounders. Similar results were observed when sensitivity analyses were performed. There was also a non-linear relationship between FI and all-cause mortality. In a weighted multivariate COX proportional model adjusted for full confounders, frailty T2DM increased all-cause (HR, 1.86; 95% CI 1.55-2.24; P < 0.0001) and cardiovascular (HR 1.66; 95% CI 1.18-2.33; P = 0.003) mortality and compared to non-frailty T2DM. The positive association of frailty index and all-cause mortality was only in participants without CHF. The positive association of frailty index and cardiovascular mortality was only in non-anti-diabetic drug users. CONCLUSIONS: Frailty index in T2DM was positively associated with CHF in linear fashions. The Frailty index was positively correlated with all-cause and cardiovascular death in patients with T2DM. Frailty T2DM was positively associated with CHF, all-cause mortality, and cardiovascular mortality compared to non-frailty T2DM. Promoting frailty measurement and management in T2DM may be beneficial to reduce the burden of CHF and mortality.
ABSTRACT
Liver cirrhosis is a confirmed risk factor for poor prognosis of stroke; however, the contribution of clinically inapparent liver fibrosis to cardioembolic stroke (CES) and its outcomes are poorly understood. This study aimed to investigate the associations between liver fibrosis-measured by the Fibrosis-4 (FIB-4) score-and stroke severity and short-term clinical outcomes of patients with acute CES due to nonvalvular atrial fibrillation (NVAF). A total of 522 patients were followed for a median of 90 days. We calculated the FIB-4 score and defined liver fibrosis as follows: likely advanced fibrosis (FIB-4 > 3.25), indeterminate advanced fibrosis (FIB-4, 1.45-3.25), and unlikely advanced fibrosis (FIB-4 < 1.45). Logistic regression analysis and Cox regression analysis were used to investigate the relations between the FIB-4 score and stroke severity, major disability at discharge, and all-cause mortality. Among these 522 acute CES patients with NVAF, the mean FIB-4 score (2.28) on admission reflected intermediate fibrosis, whereas liver enzymes were largely normal. In multivariate regression analysis, patients with advanced liver fibrosis were more likely to have a higher risk of severe stroke (OR = 2.21, 95% CI 1.04-3.54), major disability at discharge (OR = 4.59, 95% CI 1.88-11.18), and all-cause mortality (HR = 1.25, 95% CI 1.10-1.56) than their counterparts. Regarding sex, these associations were stronger in males but not significant in females. In patients with acute CES due to NVAF, advanced liver fibrosis is associated with severe stroke, major disability, and all-cause death. Our findings indicate that early screening and management of liver fibrosis may decrease stroke severity and risk of death in patients with NVAF, especially for male patients. Consequently, FIB-4 > 3.25 of male patients should receive ultrasound elastography to further determine the degree of liver fibrosis.
