Targeting inflammation in atherosclerosis: overview, strategy and directions.

Atherosclerosis is a chronic condition characterised by the build-up of plaque in the inner lining of the blood vessels and it is the main underlying cause of cardiovascular disease. The development of atherosclerosis is associated with the accumulation of cholesterol and inflammation. Although effective therapies exist to lower low-density lipoprotein cholesterol (LDL-C) levels, some patients still experience cardiovascular events due to persistent inflammation, known as residual inflammatory risk (RIR). Researchers have conducted laboratory and animal studies to investigate the measurement and targeting of the inflammatory cascade associated with atherosclerosis, which have yielded promising results. In addition to guideline-directed lifestyle modifications and optimal medical therapy focusing on reducing LDL-C levels, pharmacological interventions targeting inflammation may provide further assistance in preventing future cardiac events. This review aims to explain the mechanisms of inflammation in atherosclerosis, identifies potential biomarkers, discusses available therapeutic options and their strengths and limitations, highlights future advancements, and summarises notable clinical studies. Finally, an evaluation and management algorithm for addressing RIR is presented.

Association of blood viscosity and device-free days among hospitalized patients with COVID-19.

BACKGROUND: Increased estimated whole blood viscosity (eWBV) predicts higher mortality in patients hospitalized for coronavirus disease 2019 (COVID-19). This study assesses whether eWBV is an early predictor of non-fatal outcomes among patients hospitalized for acute COVID-19 infection. METHODS: This retrospective cohort study included 9278 hospitalized COVID-19 patients diagnosed within 48 h of admission between February 27, 2020 to November 20, 2021 within the Mount Sinai Health System in New York City. Patients with missing values for major covariates, discharge information, and those who failed to meet the criteria for the non-Newtonian blood model were excluded. 5621 participants were included in the main analysis. Additional analyses were performed separately for 4352 participants who had measurements of white blood cell count, C-reactive protein and D-dimer. Participants were divided into quartiles based on estimated high-shear blood viscosity (eHSBV) and estimated low-shear blood viscosity (eLSBV). Blood viscosity was calculated using the Walburn-Schneck model. The primary outcome was evaluated as an ordinal scale indicating the number of days free of respiratory organ support through day 21, and those who died in-hospital were assigned a value of -1. Multivariate cumulative logistic regression was conducted to evaluate the association between quartiles of eWBV and events. RESULTS: Among 5621 participants, 3459 (61.5%) were male with mean age of 63.2 (SD 17.1) years. The linear modeling yielded an adjusted odds ratio (aOR) of 0.68 (95% CI 0.59-0.79, p value < 0.001) per 1 centipoise increase in eHSBV. CONCLUSIONS: Among hospitalized patients with COVID-19, elevated eHSBV and eLSBV at presentation were associated with an increased need for respiratory organ support at 21 days. These findings are highly relevant, as they demonstrate the utility of eWBV in identifying hospitalized patients with acute COVID-19 infection at increased risk for non-fatal outcomes in early stages of the disease.

Clinical Trial Design for Triglyceride-Rich Lipoprotein-Lowering Therapies: JACC Focus Seminar 3/3.

Triglyceride-rich lipoproteins (TRLs) are a source of residual risk in patients with atherosclerotic cardiovascular disease, and are indirectly correlated with triglyceride (TG) levels. Previous clinical trials studying TG-lowering therapies have either failed to reduce major adverse cardiovascular events or shown no linkage of TG reduction with event reduction, particularly when these agents were tested on a background of statin therapy. Limitations in trial design may explain this lack of efficacy. With the advent of new RNA-silencing therapies in the TG metabolism pathway, there is renewed focus on reducing TRLs for major adverse cardiovascular event reduction. In this context, the pathophysiology of TRLs, pharmacological effects of TRL-lowering therapies, and optimal design of cardiovascular outcomes trials are major considerations.

Lipoprotein-X and Lipoprotein-Z Induced Hyperviscosity Syndrome in the Setting of Cholestatic Liver Failure.

We describe a case referred for worsening hypercholesterolemia in the setting of atorvastatin and fenofibrate-induced liver injury. The patient reported neurological complaints attributed to hyperviscosity syndrome (induced by lipoprotein-X and lipoprotein-Z). Hepatic recovery was associated with reduction of whole blood viscosity and amelioration of neurological symptoms. (Level of Difficulty: Advanced.).

Association of Blood Viscosity With Mortality Among Patients Hospitalized With COVID-19.

BACKGROUND: Coronavirus disease-2019 (COVID-19) is characterized by a dysfunctional immune response and abnormal blood rheology that contribute to endothelial dysfunction and thrombotic complications. Whole blood viscosity (WBV) is a clinically validated measure of blood rheology and an established predictor of cardiovascular risk. We hypothesize that increased WBV is associated with mortality among patients hospitalized with COVID-19. OBJECTIVES: This study sought to determine the association between estimated BV (eBV) and mortality among hospitalized COVID-19 patients. METHODS: The study population included 5,621 hospitalized COVID-19 patients at the Mount Sinai Health System from February 27, 2020, to November 27, 2021. eBV was calculated using the Walburn-Schneck model. Multivariate Cox proportional hazards models were used to evaluate the association between eBV and mortality. Considered covariates included age, sex, race, cardiovascular and metabolic comorbidities, in-house pharmacotherapy, and baseline inflammatory biomarkers. RESULTS: Estimated high-shear BV (eHSBV) and estimated low-shear BV were associated with increased in-hospital mortality. One-centipoise increases in eHSBV and estimated low-shear BV were associated with a 36.0% and 7.0% increase in death, respectively (P < 0.001). Compared with participants in the lowest quartile of eHSBV, those in the highest quartile of eHSBV had higher mortality (adjusted HR: 1.53; 95% CI: 1.27-1.84). The association was consistent among multiple subgroups, notably among patients without any comorbidities (adjusted HR: 1.69; 95% CI: 1.28-2.22). CONCLUSIONS: Among hospitalized COVID-19 patients, increased eBV is significantly associated with higher mortality. This suggests that eBV can prognosticate patient outcomes in earlier stages of COVID-19, and that future therapeutics aimed at reducing WBV should be evaluated.