Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease

BACKGROUND: Free radical scavengers have failed to improve patient outcomes, promoting the concept that clinically important oxidative stress may be mediated by alternative mechanisms. We sought to examine the association of emerging aminothiol markers of nonfree radical mediated oxidative stress with clinical outcomes. METHODS AND RESULTS: Plasma levels of reduced (cysteine and glutathione) and oxidized (cystine and glutathione disulphide) aminothiols were quantified by high performance liquid chromatography in 1411 patients undergoing coronary angiography (mean age 63 years, male 66%). All patients were followed for a mean of 4.7 +/- 2.1 years for the primary outcome of all-cause death (n=247). Levels of cystine (oxidized) and glutathione (reduced) were associated with risk of death (P+1 SD and CONCLUSIONS: A high burden of oxidative stress, quantified by the plasma aminothiols, cystine, glutathione, and their ratio, is associated with mortality in patients with coronary artery disease, a finding that is independent of and additive to the inflammatory burden. Importantly, these data support the emerging role of nonfree radical biology in driving clinically important oxidative stress

Employee Perceptions on Ethics, Racial-Ethnic and Work Disparities in Long-Term Care: Implications for Ethics Committees

This study explored the perceptions of ethics among long-term care employees (N275) in order to test two hypotheses. A cohort cross-sectional survey examined employees’ perceptions of an ethics environment, racial-ethnic, and position disparities (HO1; ANOVA), and, secondarily, ethics in relationship to select, research-grounded work features measured as manage disagreements, effectiveness, work satisfaction, and opinions of care, the latter including intention to remain (HO2; Pearson Correlations). Established questionnaires with robust psychometrics were employed. Response rate was 51%. Non-significant differences between sample and population on key variables supported extrapolation of results. Statistically significant differences between racial–ethnic (p \u3c 0.03; F 2.42) and work positions (p \u3c0.0001; F 6.24) were revealed on ethics (3.16; HO1). Statistically significant relationships (p \u3c0.0001; r = 0.26–0.68; HO2) between ethics and employees’ work features also were found, confirming both hypotheses. Perceptions of ethics based on racial-ethnic and position disparities, as well as the robust links with employee work features, offered potential avenues for decreasing disparities at work and improving the quality of long-term care. Noted further on ethics item scoring were relatively low scores indicating less involvement in, and access to, ethics discussions and decisions. In contrast, the literature review substantiated the importance of empowerment and retention, which were enhanced by employee involvement in work, notably, discussions and decisions. Thus, implications of ethics committees in long-term care sites as ways to potentially enhance employees’ work and quality of care, especially work satisfaction and retention, were explored; relevant concerns raised by the Covid pandemic were, briefly, discussed

Economic Evaluation of PCSK9 Inhibitors in Reducing Cardiovascular Risk from Health System and Private Payer Perspectives

The introduction of Proprotein covertase subtilisin/kexin type 9 (PCSK9) inhibitors has been heralded as a major advancement in reducing low-density lipoprotein cholesterol levels by nearly 50%. However, concerns have been raised on the added value to the health care system in terms of their costs and benefits. We assess the cost-effectiveness of PCSK9 inhibitors based on a decision-analytic model with existing clinical evidence. The model compares a lipid-lowering therapy based on statin plus PCSK9 inhibitor treatment with statin treatment only (standard therapy). From health system perspective, incremental cost per quality adjusted life years (QALYs) gained are presented. From a private payer perspective, return-on-investment and net present values over patient lifespan are presented. At the current annual cost of $14,000 to$15,000, PCSK9 inhibitors are not cost-effective at an incremental cost of about $350,000 per QALY. Moreover, for every dollar invested in PCSK9 inhibitors, the private payer loses$1.98. Our study suggests that the annual treatment price should be set at $4,250 at a societal willingness-to-pay of$100,000 per QALY. However, we estimate the breakeven price for private payer is only $600 per annual treatment. At current prices, our study suggests that PCSK9 inhibitors do not add value to the U.S. health system and their provision is not profitable for private payers. To be the breakthrough drug in the fight against cardiovascular disease, the current price of PCSK9 inhibitors must be reduced by more than 70%

Lipoprotein Sub-Fractions by Ion-Mobility Analysis and Its Association with Subclinical Coronary Atherosclerosis in High-Risk Individuals

AIMS: There is limited knowledge about the association of lipoprotein particles and markers of coronary atherosclerosis such as coronary artery calcification (CAC) in relatively young high-risk persons. This study examines the association of lipoprotein subfractions and CAC in high cardiometabolic risk individuals. METHODS: The study presents analysis from baseline data of a randomized trial targeted at high-risk workers. Employees of Baptist Health South Florida with metabolic syndrome or diabetes were recruited. At baseline, all 182 participants had lipoprotein subfraction analysis using the ion mobility technique and participants above 35 years (N=170) had CAC test done. Principal components (PC) were computed for the combination of lipoprotein subclasses. Multiple bootstrapped regression analyses (BSA) were conducted to assess the relationship between lipoprotein subfractions and CAC. RESULTS: The study population (N=170) was largely female (84%) with a mean age of 58 years. Three PCs accounted for 88% variation in the sample. PC2, with main contributions from VLDL particles in the positive direction and large LDL particles in the negative direction was associated with a 22% increase in CAC odds (P value ＜0.05 in 100% of BSA). PC3, with main contributions from HDL lipoprotein particles in the positive direction and small/medium LDL and large IDL particles in the negative direction, was associated with a 9% reduction in CAC odds (P＜0.05 in 88% of BSA). PC1, which had approximately even contributions from HDL, LDL, IDL and VLDL lipoprotein subfractions in the positive direction, was not associated with CAC. CONCLUSION: In a relatively young but high-risk population, a lipoprotein profile predominated by triglyceride-rich lipoproteins was associated with increased risk of CAC, while one predominated by HDL lipoproteins offered modest protection. Lipoprotein sub-fraction analysis may help to further discriminate patients who require more intensive cardiovascular work-up and treatment

Performance of A Metabolomic Biomarker Score Compared to Three Prognostic Scores in Chronic Heart Failure

The Cardiac Lipid Panel (CLP) is a novel panel of metabolomic biomarkers that has previously shown to improve the diagnostic and prognostic value for CHF patients. Several prognostic scores have been developed for cardiovascular disease (CVD) risk, but their use is limited to specific populations and precision is still inadequate. We compared a risk score using the CLP plus NT-proBNP to three commonly used risk scores: The Seattle Heart Failure Model (SHFM), Framingham Risk Score (FRS), and Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score. We included 280 elderly CHF patients from the Cardiac Insufficiency Bisoprolol Study in Elderly (CIBIS-ELD) trial. Cox Regression and hierarchical cluster analysis was performed. Integrated area under the curves (IAUC) was used as criterium for comparison. The mean (SD) follow-up period was 81 (33) months, and 95 (34%) subjects met the primary endpoint. The IAUC for FRS was 0.53, SHFM 0.61, MAGGIC 0.68, and CLP 0.78. Subjects were partitioned into three risk clusters: low, moderate, high with the CLP score showing the best ability to group patients into their respective risk cluster. A risk score composed of a novel panel of metabolite biomarkers plus NT-proBNP outperformed other common prognostic scores in predicting 10-year cardiovascular death in elderly ambulatory CHF patients. This approach could improve the clinical risk assessment of CHF patients. Keywords: CLP, CHF, chronic, prognosti