Haptoglobin genotype is a risk factor for coronary artery disease in prediabetes: A case-control study.

Objective: Coronary artery disease (CAD) prediction remains inconsistent with many unappreciated risk factors. Haptoglobin genotype determines the haptoglobin protein's effectiveness to bind free hemoglobin and prevent oxidative stress, a contributor to atherosclerosis. The haptoglobin 2-2 genotype increases the prevalence of cardiovascular disease (CVD) approximately five times compared to the 1-1 genotype in individuals with diabetes. The risk is unknown in prediabetes. The purpose of this study was to determine an association between haptoglobin genotype and CAD in prediabetes. Methods: The researchers used case-control convenience sampling from two cardiovascular disease prevention clinics in Memphis, TN, and Spokane, WA, from January 1, 2016 to March 31, 2020. Participants were ages 35-70, had prediabetes, and free of chronic inflammatory or infectious diseases. Cases had a history of subclinical or clinical CAD, while controls did not have a history of CAD. Differences between cases and controls and among haptoglobin genotypes were analyzed using t-tests and ANOVA for continuous variables and chi-square or Fisher's exact tests for categorical variables. Associations among Hp genotypes and CAD were estimated using logistic regression. Results: The sample (N = 178; 72 cases and 106 controls) was 96 % white and 64 % male. Cases had lower total cholesterol (p = 0.0001) and high-sensitivity C-reactive protein (p = 0.021). Except for CAD, haptoglobin genotype was independent of any demographic or clinical variable. Haptoglobin 2-2 genotype had 4.0 times higher odds of CAD than haptoglobin 1-1 (p = 0.01). Conclusion: Haptoglobin 2-2 genotype had approximately four times higher odds of having CAD compared to the haptoglobin 1-1 genotype. Cases had more desirable clinical profiles, likely attributable to more aggressive treatment of traditional risk factors than controls. Haptoglobin genotype is a potentially important CAD risk factor in prediabetes (88 million Americans). Further studies are needed for interventions to reduce the oxidative stress associated with the Hp 2-2 genotype and glycosylated hemoglobin and for CAD reduction.

Clinical utility of inflammatory and genetic biomarkers for cardiovascular disease prevention, categorization, and treatment.

ABSTRACT: The complex interplay of increased atherogenic lipoproteins, inflammation, and immune activation hallmarks the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). Atherosclerotic cardiovascular disease remains a leading cause of death, yet risk estimator tools lack comprehensiveness for genetic/inflammatory biomarkers associated with ASCVD. Unexplained ASCVD risk necessitates a better understanding of primary, secondary, and tertiary prevention variables. This article discusses the clinical utility of genetic and inflammatory biomarkers for ASCVD risk prediction, management, treatment, and recategorization into primary, secondary, and tertiary prevention. Furthermore, nurse practitioners (NPs) should use a ternary prevention classification system instead of the current binary system to mitigate risk in the large group of patients with subclinical ASCVD. High-sensitivity C-reactive protein (hs-CRP)-linearly associated with ASCVD-and lipoprotein-associated phospholipase-A 2 (Lp-PLA 2 ) and myeloperoxidase (MPO), both associated with plaque vulnerability/rupture, are inflammatory biomarkers. Elevated hs-CRP, MPO, and Lp-PLA 2 treatment requires addressing root causes of elevation (e.g., obesity, insulin resistance, tobacco use, gingival disease, and chronic autoimmune/infectious conditions). In addition, haptoglobin (Hp) phenotype determines the antioxidant potential of Hp. Haptoglobin phenotype, a root cause of ASCVD, is a one-time test. Individuals with Hp 2-2 should adopt a gluten-free diet to reduce endothelial and intestinal inflammation. Nurse practitioners should use stricter glycemic goals (hemoglobin A1c ≤6.5%) and add daily vitamin E if this group has type 2 diabetes. Genetic/inflammatory biomarkers should be used to better predict ASCVD risk and tailor primary, secondary, and tertiary prevention treatment. Clinical use of these biomarkers reaches beyond the standard of care to reduce residual ASCVD risk.

Oxidative Stress Underpins Clinical, Social, and Genetic Risk Factors for Atherosclerotic Cardiovascular Disease.

Background: Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide and is poorly predicted with current risk estimation tools. The biological mechanisms relating ASCVD risk factors to oxidative stress (OS) and how this accumulates ASCVD risk are misunderstood. Purpose: To develop a comprehensive conceptual model explaining how expanded clinical, social, and genetic ASCVD risk factors accumulate ASCVD risk through OS. Conclusions: OS (primarily from excess reactive oxygen species) and inflammation are present along the entire ASCVD pathophysiologic continuum. An expanded list of clinical and social ASCVD risk factors (including hypertension, obesity, diabetes, kidney disease, inflammatory diseases, substance use, poor nutrition, psychosocial stress, air pollution, race, and genetic ancestry) influence ASCVD largely through increased OS. Many risk factors exert a positive feedback mechanism to increase OS. One genetic risk factor, haptoglobin (Hp) genotype, is associated with higher ASCVD risk in diabetes and hypothesized to do the same in those with insulin resistance due to the Hp 2-2 genotype increasing OS. Implications: Understanding the biological mechanisms of OS informs how these ASCVD risk factors relate to each other and compound ASCVD risk. Individualized ASCVD risk estimation should include a comprehensive, holistic perspective of risk factors to better address the clinical, social, and genetic influences of OS. Preventing and reducing OS is key to preventing ASCVD development or progression.

Examining moral injury in clinical practice: A narrative literature review.

Healthcare workers experience moral injury (MI), a violation of their moral code due to circumstances beyond their control. MI threatens the healthcare workforce in all settings and leads to medical errors, depression/anxiety, and personal and occupational dysfunction, significantly affecting job satisfaction and retention. This article aims to differentiate concepts and define causes surrounding MI in healthcare. A narrative literature review was performed using SCOPUS, CINAHL, and PubMed for peer-reviewed journal articles published in English between 2017 and 2023. Search terms included "moral injury" and "moral distress," identifying 249 records. While individual risk factors predispose healthcare workers to MI, root causes stem from healthcare systems. Accumulation of moral stressors and potentially morally injurious events (PMIEs) (from administrative burden, institutional betrayal, lack of autonomy, corporatization of healthcare, and inadequate resources) result in MI. Individuals with MI develop moral resilience or residue, leading to burnout, job abandonment, and post-traumatic stress. Healthcare institutions should focus on administrative and climate interventions to prevent and address MI. Management should ensure autonomy, provide tangible support, reduce administrative burden, advocate for diversity of clinical healthcare roles in positions of interdisciplinary leadership, and communicate effectively. Strategies also exist for individuals to increase moral resilience, reducing the impact of moral stressors and PMIEs.