Background: There is a paucity of evidence regarding the association between visit‐to‐visit blood pressure variability and residual cardiovascular risk. We aimed to provide relevant evidence by determining whether high systolic blood pressure (SBP) variability in the optimal SBP levels still influences the risk of cardiovascular disease. Methods and Results: We studied 7065 participants (aged 59.3±5.6 years; 44.3% men; and 82.9% White) in the ARIC (Atherosclerosis Risk in Communities) study with optimal SBP levels from visit 1 to visit 3. Visit‐to‐visit SBP variability was measured by variability independent of the mean in the primary analysis. The primary outcome was the major adverse cardiovascular event (MACE), defined as the first occurrence of all‐cause mortality, coronary heart disease, stroke, and heart failure. During a median follow‐up of 19.6 years, 2691 participants developed MACEs. After multivariable adjustment, the MACE risk was higher by 21% in participants with the highest SBP variability (variability independent of the mean quartile 4) compared with the lowest SBP variability participants (variability independent of the mean quartile 1) (hazard ratio, 1.21; 95% CI, 1.09–1.35). The restricted cubic spline showed that the hazard ratio for MACE was relatively linear, with a higher variability independent of the mean being associated with higher risk. These association were also found in the stratified analyses of participants with or without hypertension. Conclusions: In adults with optimal SBP levels, higher visit‐to‐visit SBP variability was significantly associated with a higher risk of MACE regardless of whether they had hypertension. Therefore, it may be necessary to further focus on the visit‐to‐visit SBP variability even at the guideline‐recommended optimal blood pressure levels.

Hyperglycemia serves an important role in the pathogenesis of diabetic cardiomyopathy. The aim of the present study was to investigate whether exogenous hydrogen sulfide (H2S) protects against high glucose‑induced inflammation and cytotoxicity in cardiac cells by inhibiting the p38 mitogen‑activated protein kinase (MAPK)/nuclear factor‑κB (NF‑κB), cyclooxygenase‑2 (COX‑2) and inducible nitric oxide synthase (iNOS) signaling pathways. Rat H9c2 myocardium cells were exposed to 33 mM glucose (high glucose, HG) for 24 h to stimulate HG‑induced cytotoxicity. One group of cells was pretreated with NaHS (a donor of H2S) prior to HG exposure, and cell viability was determined using the Cell Counting Kit‑8 assay. The protein expression levels of p38MAPK, the phosphorylated p65 subunit of NF‑κB, iNOS, COX‑2 and caspase‑3 were analyzed by western blotting, and the protein expression levels of interleukin (IL)‑1β and IL‑6 were detected by enzyme‑linked immunosorbent assay (ELISA). Pretreatment of H9c2 cells with NaHS for 30 min prior to exposure to HG significantly ameliorated the expression of p38MAPK and NF‑κB. In addition, pretreatment with NaHS markedly attenuated p38MAPK/NF‑κB‑mediated cytotoxicity and inflammation, as evidenced by the significant increase in cell viability and decrease in iNOS, COX‑2, IL‑1β and IL‑6 expression levels. Furthermore, treatment of cells with NaHS significantly decreased the expression of caspase‑3, which suggested that NaHS attenuated HG‑induced apoptosis. In conclusion, the results of the present study provided evidence to suggest that exogenous H2S protects against HG‑induced cytotoxicity and inflammation in H9c2 cardiac cells. H2S may exert these cytoprotective effects via inhibition of the p38MAPK/NF‑κB, COX‑2 and iNOS signaling pathways.

Thalidomide is effective in inducing and maintaining clinical remission, as well as mucosal healing, in patients with refractory Crohn’s disease (CD). However, long-term use of thalidomide has raised concern because of the high incidence of adverse events. Cardiovascular events induced by thalidomide have been reported in patients with multiple myeloma, amyotrophic lateral sclerosis, and transfusion-dependent refractory anemia. We report here an extremely rare case of sinus bradycardia induced by thalidomide in an adult patient with CD. This patient’s heart rate converted back to a normal sinus rhythm after withdrawal of thalidomide, but recurred after restarting of thalidomide. Cardiac toxicity should be closely monitored when using thalidomide in patients with CD.

Background and aims: Standard 12-lead electrocardiogram (ECG) patterns combined with the anatomical cardiac long-axis angle revealed by chest X-ray can prevent the influence of cardiac rotation, physical shape, and lead position, so it may be an ideal means to predict the origin of the outflow tract (OT) ventricular arrhythmias (OTVAs) for ablation procedures. The study explores the value of this strategy in identifying the origin of OTVA.Methods: This study was conducted using a retrospective cohort and a prospective cohort of consecutive patients at two centers. The anatomical cardiac long-axis angle was calculated by measuring the angle between the cardiac long-axis (a line joining the apex to the midpoint of the mitral annulus) and the horizontal plane on a chest X-ray. The V2S angle was calculated as the V2S amplitude times the angle. We ultimately enrolled 147 patients with symptomatic OTVAs who underwent successful radiofrequency catheter ablation (RFCA) (98 women (66.7%); mean age 46.9 ± 14.7 years; 126 right ventricular OT (RVOT) origins, 21 left ventricular OT (LVOT) origins) as a development cohort. The new algorithm was validated in 48 prospective patients (12 men (25.0%); mean age 48.0 ± 15.8 years; 36 RVOT, 12 LVOT origins).Results: Patients with RVOT VAs had greater V2S, long-axis angle, and V2S angle than patients with LVOT VA (all P < 0.001). The cut-off V2S angle obtained by receiver operating characteristic (ROC) curve analysis was 58.28 mV° for the prediction of RVOT origin (sensitivity: 85.7%; specificity: 95.2%; positive predictive value: 99.1%; negative predictive value: 52.6%). The AUC achieved using the V2S angle was 0.888 (P < 0.001), which was the highest among all indexes (V2S/V3R: 0.887 (P < 0.016); TZ index: 0.858 (P < 0.001); V1-2 SRd: 0.876 (P < 0.001); V3 transition: 0.651 (P < 0.001)). In the prospective cohort, the V2S angle had a high overall accuracy of 93.8% and decreased the procedure time (P = 0.002).Conclusion: V2S angle can be a novel measure that can be used to accurately differentiate RVOT from LVOT origins. It could help decrease ablation duration and radiation exposure.