Different blood flow patterns in the arteries can alter the adaptive phenotype of vascular endothelial cells (ECs), thereby affecting the functions of ECs and are directly associated with the occurrence of lesions in the early stages of atherosclerosis (AS). Atherosclerotic plaques are commonly found at curved or bifurcated arteries, where the blood flow pattern is dominated by oscillating shear stress (OSS). OSS can induce ECs to transform into pro-inflammatory phenotypes, increase cellular inflammation, oxidative stress response, mitochondrial dysfunction, metabolic abnormalities and endothelial permeability, thereby promoting the progression of AS. On the other hand, the straight artery has a stable laminar shear stress (LSS), which promotes the transformation of ECs into an anti-inflammatory phenotype, improves endothelial cell function, thereby inhibits atherosclerotic progression. ECs have the ability to actively sense, integrate, and convert mechanical stimuli by shear stress into biochemical signals that further induces intracellular changes (such as the opening and closing of ion channels, activation and transcription of signaling pathways). Here we not only outline the relationship between functions of vascular ECs and different forms of fluid shear stress in AS, but also aim to provide new solutions for potential atherosclerotic therapies targeting intracellular mechanical transductions.

Background/Objectives: The hemoglobin-to-red blood cell distribution width (RDW) ratio (HRR) reflects the status of inflammation and oxidative stress size. Previously, it has been suggested that HRR is associated with cardiovascular diseases (CVD). However, evidence has been limited for examining the association between HRR and the incidence of specific cardiovascular events (e.g., cardiovascular disease, stroke, congestive heart failure) and all-cause cardiovascular death and non-cardiovascular death, adjusting for known confounders. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) in the year cycle of 1999–2018 were collected. HRR was calculated as the ratio of hemoglobin divided by the RDW. The outcomes were CVD, including stroke, congestive heart failure, atherosclerotic cardiovascular diseases (ASCVD), coronary artery disease as well as all-cause death including cardiovascular death and non-cardiovascular death. Univariate and multivariate analyses were performed to explore the association between HRR and outcomes. Restricted cubic spline curves were delineated. Results: In total, 47,719 participants were eligible for further analysis. In multivariate analysis adjusting for all confounding factors, higher HRR levels were significantly associated with a decreased risk of CVD. Compared to Q1 (<9.86), the odds ratio (OR) and 95% confidence intervals (95% CI) in Q2 (9.86–10.96), Q3 (10.96–11.97), and Q4 (≥11.97) were 0.79 (0.66, 0.94), 0.59 (0.48, 0.73), and 0.53, (0.42, 0.67), respectively, for predicting CVD. Similar results were observed for different subtypes of CVD, including stroke, congestive heart failure, and ASCVD. Notably, for predicting coronary heart disease, only Q3 was significant compared to Q1 (0.70, [0.54, 0.92], p = 0.010). HRR was significant for predicting all-cause death, cardiovascular death, and non-cardiovascular death. Additionally, HRR had the highest discriminative ability for predicting all-cause death compared with that of hemoglobin and RDW. Conclusions: A higher HRR was associated with a lower risk of CVD and death. Moderate levels of HRR were associated with the lowest risk for coronary heart disease. HRR had better discriminative ability than hemoglobin and RDW.