Although there are conflicting guideline recommendations for the control of blood pressure (BP), evidence from a meta-analysis of 4 trials in patients with hypertension 65 years and older has shown that intensive BP control could reduce the risk of cardiovascular events.¹ This was supported by another 2 meta-analyses demonstrating that a lower systolic BP was associated with better cardiovascular outcomes across all age groups.^2,3 More recently, results of patients aged 60 to 80 years from the STEP (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients) trial indicated that intensive treatment to target a systolic BP of 110 to 130 mm Hg reduced the risk of cardiovascular events compared with standard treatment with a target of 130 to 150 mm Hg.⁴

Blood pressure (BP) is a continuous and dynamic measure. However, standard BP control metrics may not reflect the variability in BP over time. This study assessed the prognostic value of time in BP target range among hypertensive patients with heart failure (HF). The authors performed a post hoc analysis of data from the TOPCAT (Treatment of Preserved Cardiac Function HF with an Aldosterone Antagonist) trial and the BEST (Beta-Blocker Evaluation of Survival Trial). Time in target range (TTR) for each patient was calculated using linear interpolation across the study period with the target range of systolic BP between 120 and 130 mm Hg. A total of 4,789 hypertensive patients (n = 1,654 from BEST and n = 3,135 from TOPCAT) were included. The cumulative incidences of primary endpoint (ie, cardiovascular death or HF hospitalization) were highest among the top quartile of TTR with a dose-dependent manner across quartiles (P_trend <0.005). The top quartile of TTR was significantly associated with a lower risk of primary outcome using adjusted Cox regression model (HR: 0.71; 95% CI: 0.60-0.82), cardiovascular mortality (HR: 0.68; 95% CI: 0.55-0.84), HF hospitalization (HR: 0.70; 95% CI: 0.58-0.85), all-cause mortality (HR: 0.69; 95% CI: 0.58-0.83), and any hospitalization (HR: 0.76; 95% CI: 0.67-0.85). Further analyses using restricted cubic spline indicated a linear relationship between TTR and primary outcome. Similar patterns were observed in the individual trial. Sensitivity analyses generated consistent results while redefining target range as 110 to 130 mm Hg for systolic BP or 70 to 80 mm Hg for diastolic BP. TTR could independently predict major adverse cardiovascular events in hypertensive patients with HF.

Aims: The present study aimed to investigate alterations in neuroinflammation after heart failure (HF) and explore the potential mechanisms.Methods: Male wild-type (WT) and Toll-like receptor 4 (TLR4)-knockout (KO) mice were subjected to sham operation or ligation of the left anterior descending coronary artery to induce HF. 8 weeks later, cardiac functions were analyzed by echocardiography, and intestinal barrier functions were examined by measuring tight junction protein expression, intestinal permeability and plasma metabolite levels. Alterations in neuroinflammation in the brain were examined by measuring microglial activation, inflammatory cytokine levels and the proinflammatory signaling pathway. The intestinal barrier protector intestinal alkaline phosphatase (IAP) and intestinal homeostasis inhibitor L-phenylalanine (L-Phe) were used to examine the relationship between intestinal barrier dysfunction and neuroinflammation in mice with HF.Results: Eight weeks later, WT mice with HF displayed obvious increases in intestinal permeability and plasma lipopolysaccharide (LPS) levels, which were accompanied by elevated expression of TLR4 in the brain and enhanced neuroinflammation. Treatment with the intestinal barrier protector IAP significantly attenuated neuroinflammation after HF while effectively increasing plasma LPS levels. TLR4-KO mice showed significant improvements in HF-induced neuroinflammation, which was not markedly affected by intestinal barrier inhibitors or protectors.Conclusion: HF could induce intestinal barrier dysfunction and increase gut-to-blood translocation of LPS, which could further promote neuroinflammation through the TLR4 pathway.