ObjectivesThis study aimed to investigate the relationship between frailty and all-cause mortality in hypertensive population.MethodsWe used data from the National Health and Nutrition Examination Survey (NHANES) 1999–2002 and mortality data from the National Death Index. Frailty was assessed using the revised version of the Fried frailty criteria (weakness, exhaustion, low physical activity, shrinking, and slowness). This study aimed to evaluate the association between frailty and all-cause mortality. Cox proportional hazard models were used to evaluate the association between frailty category and all-cause mortality, adjusted for age, sex, race, education, poverty–income ratio, smoking, alcohol, diabetes, arthritis, congestive heart failure, coronary heart disease, stroke, overweight, cancer or malignancy, chronic obstructive pulmonary disease, chronic kidney disease, and taking medicine for hypertension.ResultsWe gathered data of 2,117 participants with hypertension; 17.81%, 28.77%, and 53.42% were classified as frail, pre-frail, and robust, respectively. We found that frail [hazard ratio (HR) = 2.76, 95% confidence interval (CI) = 2.33–3.27] and pre-frail (HR = 1.38, 95% CI = 1.19–1.59] were significantly associated with all-cause mortality after controlling for variables. We found that frail (HR = 3.02, 95% CI = 2.50–3.65) and pre-frail (HR = 1.35, 95% CI = 1.15–1.58) were associated with all-cause mortality in the age group ≥65 years. For the frailty components, weakness (HR = 1.77, 95% CI = 1.55–2.03), exhaustion (HR = 2.25, 95% CI = 1.92–2.65), low physical activity (HR = 2.25, 95% CI = 1.95–2.61), shrinking (HR = 1.48, 95% CI = 1.13–1.92), and slowness (HR = 1.44, 95% CI = 1.22–1.69) were associated with all-cause mortality.ConclusionThis study demonstrated that frailty and pre-frailty were associated with an increased risk of all-cause mortality in patients with hypertension. More attention should be paid to frailty in hypertensive patients, and interventions to reduce the burden of frailty may improve outcomes in these patients.

Background. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2), a novel immunoregulatory protein, has been reported to regulate inflammation and apoptosis. The role of TIPE2 in cardiovascular disease, especially cardiac hypertrophy, has not been elucidated. Thus, the aim of the present study was to explore the role of TIPE2 in cardiac hypertrophy. Methods. Mice were subjected to aortic banding (AB) to induce an adverse hypertrophic model. To overexpress TIPE2, mice were injected with a lentiviral vector expressing TIPE2. Echocardiographic and hemodynamic analyses were used to evaluate cardiac function. Neonatal rat cardiomyocytes (NRCMs) and mouse peritoneal macrophages (MPMs) were isolated and stimulated with angiotensin II. NRCMs and MPM were also cocultured and stimulated with angiotensin II. Cells were transfected with Lenti-TIPE2 to overexpress TIPE2. Results. TIPE2 expression levels were downregulated in hypertrophic mouse hearts and in macrophages in heart tissue. TIPE2 overexpression attenuated pressure overload-induced cardiac hypertrophy, fibrosis, and cardiac dysfunction. Moreover, we found that TIPE2 overexpression in neonatal cardiomyocytes did not relieve the angiotensin II-induced hypertrophic response in vitro. Furthermore, TIPE2 overexpression downregulated TLR4 and NF-κB signaling in macrophages but not in cardiomyocytes, which led to diminished inflammation in macrophages and consequently reduced the activation of hypertrophic Akt signaling in cardiomyocytes. TLR4 inhibition by TAK-242 did not enhance the antihypertrophic effect of TIPE2 overexpression. Conclusions. The present study indicated that TIPE2 represses macrophage activation by targeting TLR4, subsequently inhibiting cardiac hypertrophy.