Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association.

Hypertriglyceridemia (triglycerides 200-499 mg/dL) is relatively common in the United States, whereas more severe triglyceride elevations (very high triglycerides, ≥500 mg/dL) are far less frequently observed. Both are becoming increasingly prevalent in the United States and elsewhere, likely driven in large part by growing rates of obesity and diabetes mellitus. In a 2002 American Heart Association scientific statement, the omega-3 fatty acids (n-3 FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were recommended (at a dose of 2-4 g/d) for reducing triglycerides in patients with elevated triglycerides. Since 2002, prescription agents containing EPA+DHA or EPA alone have been approved by the US Food and Drug Administration for treating very high triglycerides; these agents are also widely used for hypertriglyceridemia. The purpose of this advisory is to summarize the lipid and lipoprotein effects resulting from pharmacological doses of n-3 FAs (>3 g/d total EPA+DHA) on the basis of new scientific data and availability of n-3 FA agents. In treatment of very high triglycerides with 4 g/d, EPA+DHA agents reduce triglycerides by ≥30% with concurrent increases in low-density lipoprotein cholesterol, whereas EPA-only did not raise low-density lipoprotein cholesterol in very high triglycerides. When used to treat hypertriglyceridemia, n-3 FAs with EPA+DHA or with EPA-only appear roughly comparable for triglyceride lowering and do not increase low-density lipoprotein cholesterol when used as monotherapy or in combination with a statin. In the largest trials of 4 g/d prescription n-3 FA, non-high-density lipoprotein cholesterol and apolipoprotein B were modestly decreased, indicating reductions in total atherogenic lipoproteins. The use of n-3 FA (4 g/d) for improving atherosclerotic cardiovascular disease risk in patients with hypertriglyceridemia is supported by a 25% reduction in major adverse cardiovascular events in REDUCE-IT (Reduction of Cardiovascular Events With EPA Intervention Trial), a randomized placebo-controlled trial of EPA-only in high-risk patients treated with a statin. The results of a trial of 4 g/d prescription EPA+DHA in hypertriglyceridemia are anticipated in 2020. We conclude that prescription n-3 FAs (EPA+DHA or EPA-only) at a dose of 4 g/d (>3 g/d total EPA+DHA) are an effective and safe option for reducing triglycerides as monotherapy or as an adjunct to other lipid-lowering agents.

Seafood Long-Chain n-3 Polyunsaturated Fatty Acids and Cardiovascular Disease: A Science Advisory From the American Heart Association.

Since the 2002 American Heart Association scientific statement "Fish Consumption, Fish Oil, Omega-3 Fatty Acids, and Cardiovascular Disease," evidence from observational and experimental studies and from randomized controlled trials continues to emerge to further substantiate the beneficial effects of seafood long-chain n-3 polyunsaturated fatty acids and cardiovascular disease. A recent American Heart Association science advisory addressed the specific effect of n-3 polyunsaturated fatty acid supplementation on clinical cardiovascular events. This American Heart Association science advisory extends that review and offers further support to include n-3 polyunsaturated fatty acids from seafood consumption. Several potential mechanisms have been investigated, including antiarrhythmic, anti-inflammatory, hematologic, and endothelial, although for most, longer-term dietary trials of seafood are warranted to substantiate the benefit of seafood as a replacement for other important sources of macronutrients. The present science advisory reviews this evidence and makes a suggestion in the context of the 2015-2020 Dietary Guidelines for Americans and in consideration of other constituents of seafood and the impact on sustainability. We conclude that 1 to 2 seafood meals per week be included to reduce the risk of congestive heart failure, coronary heart disease, ischemic stroke, and sudden cardiac death, especially when seafood replaces the intake of less healthy foods.

Establishing the Genomic Knowledge Matrix for Nursing Science.

PURPOSE: To establish the knowledge needed to integrate the multiple branches of omics into nursing research to accelerate achieving the research recommendations of the Genomic Nursing Science Blueprint. METHODS: The creation of the Genomic Knowledge Matrix occurred in three phases. In phase 1, the Omics Nursing Science and Education Network (ONSEN) Education Workgroup completed an evidence, bioinformatics, and technology review to inform the components of the Matrix. The ONSEN Advisory Panel then reviewed and integrated revisions. Phase 3 solicited targeted public comment focused on education and research experts, and applicable revisions were made. FINDINGS: The Genomic Knowledge Matrix establishes the following content areas: cellular and molecular biology, system physiology, microbiology, and translational bioinformatics as the minimum required preparation for nurse scientists to understand omics and to integrate this knowledge into research. The Matrix also establishes levels of understanding needed to function based on the role of the nurse scientist. CONCLUSIONS: The Genomic Knowledge Matrix addresses knowledge important for nurse scientists to integrate genomics into their research. Building on prior recommendations and existing genomic competencies, the Matrix was designed to present key knowledge elements critical to understand omics that underpin health and disease. Knowledge depth varies based on the research role. CLINICAL RELEVANCE: The Genomic Knowledge Matrix provides the vital guidance for training nurse scientists in the integration of genomics. The flexibility of the Matrix also provides guidance to inform fundamental genomic content needed in core science content in undergraduate and graduate level nursing curricula.

Omega-3 Polyunsaturated Fatty Acid (Fish Oil) Supplementation and the Prevention of Clinical Cardiovascular Disease: A Science Advisory From the American Heart Association.

Multiple randomized controlled trials (RCTs) have assessed the effects of supplementation with eicosapentaenoic acid plus docosahexaenoic acid (omega-3 polyunsaturated fatty acids, commonly called fish oils) on the occurrence of clinical cardiovascular diseases. Although the effects of supplementation for the primary prevention of clinical cardiovascular events in the general population have not been examined, RCTs have assessed the role of supplementation in secondary prevention among patients with diabetes mellitus and prediabetes, patients at high risk of cardiovascular disease, and those with prevalent coronary heart disease. In this scientific advisory, we take a clinical approach and focus on common indications for omega-3 polyunsaturated fatty acid supplements related to the prevention of clinical cardiovascular events. We limited the scope of our review to large RCTs of supplementation with major clinical cardiovascular disease end points; meta-analyses were considered secondarily. We discuss the features of available RCTs and provide the rationale for our recommendations. We then use existing American Heart Association criteria to assess the strength of the recommendation and the level of evidence. On the basis of our review of the cumulative evidence from RCTs designed to assess the effect of omega-3 polyunsaturated fatty acid supplementation on clinical cardiovascular events, we update prior recommendations for patients with prevalent coronary heart disease, and we offer recommendations, when data are available, for patients with other clinical indications, including patients with diabetes mellitus and prediabetes and those with high risk of cardiovascular disease, stroke, heart failure, and atrial fibrillation.

Future translational applications from the contemporary genomics era: a scientific statement from the American Heart Association.

The field of genetics and genomics has advanced considerably with the achievement of recent milestones encompassing the identification of many loci for cardiovascular disease and variable drug responses. Despite this achievement, a gap exists in the understanding and advancement to meaningful translation that directly affects disease prevention and clinical care. The purpose of this scientific statement is to address the gap between genetic discoveries and their practical application to cardiovascular clinical care. In brief, this scientific statement assesses the current timeline for effective translation of basic discoveries to clinical advances, highlighting past successes. Current discoveries in the area of genetics and genomics are covered next, followed by future expectations, tools, and competencies for achieving the goal of improving clinical care.

A select review reporting the quality of studies measuring endothelial dysfunction in randomised diet intervention trials.

A quality assessment of the primary studies reported in the literature carried out using select dietary ingredients (DI) purported to affect vascular endothelial function was conducted through a systematic PubMed search from January 2000 to August 2012. A total of seventy randomised controlled trials with defined DI (folic acid (fifteen), n-3 fatty acids (twenty), cocoa (fifteen) and isoflavones (twenty)) and standardised measures of vascular endothelial function were evaluated. Jadad scores, quality scoring parameters for DI and flow-mediated dilation (FMD) methodology used were ascertained. A total of 3959 randomised subjects, mean age 51 (se 0·21) years (range 9-79 years), were represented in the dataset. The mean Jadad scores did not differ statistically among the DI studies, with the majority of the studies being of good quality. Higher DI quality scores were achieved by studies using the botanical ingredients cocoa and isoflavones than by those using the nutrient ingredients folic acid and n-3 fatty acids. The mean DI quality scores were 4·13 (se 0·34), 5·20 (se 0·47), 6·13 (se 0·41) and 6·00 (se 0·59) for the folic acid, n-3 fatty acid, cocoa and isoflavone intervention studies, respectively (and significantly different). The mean Corretti FMD scores were 7·27 (se 0·56), 7·46 (se 0·79), 6·29 (se 0·61) and 7·11 (se 0·56) for the folic acid, n-3 fatty acid, cocoa and isoflavone intervention studies, respectively (NS). FMD studies failed to adequately describe the equipment used and more than half failed to provide an adequate description of the procedures used for vascular image acquisition and measurement. DI can be utilised for dietary intervention studies; however, the methodology should be clearly reported using the guidelines for assessment for both DI and FMD.

The National Institute of Nursing Research Graduate Partnerships Program (NINR-GPP): an opportunity for PhD students.

The Institutional Graduate Partnerships Program (GPP) offered by the National Institute of Nursing Research (NINR) provides an exceptional opportunity for students who are enrolled in any PhD program in nursing across the nation to complete dissertation research on the premier research campus of the National Institutes of Health, Bethesda, MD. The goal of this doctoral fellowship program, which is up to 3 years in length, is to train promising doctoral students in basic and clinical research. This knowledge and skill set is necessary for the next generation of nurse scientists to ultimately conduct translational research. In this article, the authors describe the program, eligibility requirements, application procedures, and selection criteria for NINR-supported GPP nursing students. Also provided are tips for interested students and outcomes of current and former NINR-supported GPP students (NINR-GPP).

Efficacy of Polyunsaturated Fatty Acids as a Treatment for Post-traumatic Stress Disorder: A Systematic Review.

INTRODUCTION: Post-traumatic stress disorder (PTSD) is a prevalent health condition among members of the military. Although the efficacy of pharmacological and psychiatric interventions for PTSD has been well studied, there are limited data on the effects of omega-3 (n-3) polyunsaturated fatty acid (PUFA) interventions on PTSD. The use of PUFAs shows promise because of their neuroprotective effects. Thus, this systematic review will synthesize the current state of the evidence regarding the effectiveness of PUFA treatment for PTSD. MATERIALS AND METHODS: Using the PubMed, PsychINFO, Embase, and CINAHL databases, a search of the literature was conducted using the search terms "posttraumatic-stress-disorder, combat disorders, trauma-related-stress-disorder, omega-3, fatty acid, and polyunsaturated fatty acids" to identify articles published from January 1, 2008, to January 1, 2024, that focused on PUFA interventions for PTSD. A total of 281 articles were identified. Following exclusions and quality assessments using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria proposed by Cochrane, 6 randomized controlled trials (RCTs) and preclinical studies were chosen for inclusion, and data were then extracted into a data matrix for final synthesis and analysis. RESULTS: The RCTs (n = 3) showed no significant effect of PUFAs in the prevention of PTSD symptom onset. Among preclinical studies (n = 3), PUFAs resulted in a significant decrease in anxiety-like behavior and fear memory and an increase in spatial learning and memory. The quality of evidence among the 6 RCTs and preclinical studies using the Cochrane GRADE criteria ranged from low to high. CONCLUSIONS: The results from this systematic review suggest that more evidence is needed before making any recommendations for the clinical use of dietary PUFAs in the management of PTSD symptoms.

Prevalence of PTSD in Active Duty Members with Mild Traumatic Brain Injury: Systematic Review and Meta-analysis.

INTRODUCTION: Traumatic brain injury (TBI), particularly mild TBI (mTBI), is a significant health concern for U.S. active duty service members (ADSMs), with potential implications for psychiatric outcomes including PTSD. Despite recognizing this association, the prevalence of PTSD among ADSMs with mTBI remains unclear. MATERIALS AND METHODS: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A thorough search in PubMed, CINAHL, Embase, and PsycINFO databases from 2008 to 2024 focused on identifying studies involving ADSMs with PTSD and mTBI. The R software (version 4.3.2) was employed for meta-analysis with the "meta" and "meta prop" packages. RESULTS: Eight reviewed studies revealed a pooled prevalence estimate of PTSD among ADSMs with mTBI at 36% (95% CI, 30%-41%, P < .01, I2 = 96%). Cohort studies indicated a slightly higher prevalence of 38% (95% CI, 19%-59%, P < .01, I2 = 98%), whereas cross-sectional studies provided a marginally lower prevalence of 34% (95% CI, 27%-40%, P < .01, I2 = 92%). CONCLUSION: Methodological differences, including diagnostic criteria variability, contribute to the observed variability in prevalence estimates. Despite methodological challenges, this study provides crucial insights into the pooled prevalence of comorbid PTSD and mTBI within the military, emphasizing the need for standardized methodologies and further research to refine understanding and support strategies for affected individuals.

Baseline eHealth Behaviors of Service Members: A Retrospective, Cross-Sectional Analysis of Patient Portal Use Before the Pandemic.

INTRODUCTION: The use of electronic health (eHealth) tools has the potential to support the overall health, wellness, fitness status, and ability to deploy worldwide of active duty service members (SMs). Additionally, the Coronavirus Disease 2019 pandemic forced healthcare organizations to quickly convert to virtual care settings to decrease face-to-face interactions and increase access to healthcare using technology. The shift to virtual care and the push to increase use of eHealth tools heightened the need to understand how military members interact with eHealth tools. Little is known about the factors that influence SMs use of eHealth tools and if having a health condition increases or decreases use. To evaluate these factors, we completed a cross-sectional, retrospective analysis on a sample of 198,388 active duty SMs aged 18 to 68 years. MATERIALS AND METHODS: We used two Military Health System (MHS) data sources-Tricare Online (TOL) Patient Portal 2018 audit logs and outpatient electronic health record data. Using eHealth behaviors identified in the audit logs, we evaluated and compared individual characteristics (i.e., "gender", "age", "race", and "marital status"), environmental factors (i.e., "rank", "military branch", and "geographic location"), and six available health conditions (i.e., congenital health defects, amputation, anxiety, sleep, traumatic brain injury, and depression). Since moderate usage of eHealth tools is linked to improved health outcomes, adherence, communication, and increased consumer satisfaction, a logistic regression model was developed to find the factors most associated with moderate (3-11 logins per year) use of the portal. RESULTS: Electronic health use increased by SMs with underlying health conditions or if they were managing family member health. Most SMs who used the TOL Patient Portal were of ages 25-34 years, White, and married. The mean age is 32.53 for males and 29.98 for females. Over half of the TOL Patient Portal SM users utilized the portal one to two times. Most SMs used the TOL Patient Portal in Virginia, Texas, California, Florida, North Carolina, Georgia, and Maryland. The highest use was during the months of March to May. Frequent patient portal actions include searching for appointments, viewing health information, viewing medical encounters, and refilling medications. Although SMs with congenital health defects, anxiety, sleep issues, and depression have higher patient portal use rates, SMs with depression have a negative association with using the patient portal at a "moderate" rate. Viewing family member health information and searching for appointments were strongly associated with patient portal moderate use. CONCLUSIONS: Our findings support top military initiatives to improve the overall health, wellness, and readiness of SMs while decreasing the MHS's overall cost of care while providing a foundation to compare "pre" and "post" pandemic eHealth behaviors. It is essential to note that SMs are more likely to use a patient portal to seek information or manage family member health. This key factor identifies the significance of family health promotion and readiness in the active duty SM's life. The long-term goal of our study is to build the foundation for delivering tailored health information and eHealth tools to promote health and readiness-centric patient engagement.

The emerging role of flavonoid-rich cocoa and chocolate in cardiovascular health and disease.

Cocoa and chocolate have recently been found to be rich plant-derived sources of antioxidant flavonoids with beneficial cardiovascular properties. These favorable physiological effects include: antioxidant activity, vasodilation and blood pressure reduction, inhibition of platelet activity, and decreased inflammation. Increasing evidence from experimental and clinical studies using cocoa-derived products and chocolate suggest an important role for these high-flavanol-containing foods in heart and vascular protection.

Antioxidant vitamins C and E improve endothelial function in children with hyperlipidemia: Endothelial Assessment of Risk from Lipids in Youth (EARLY) Trial.

BACKGROUND: Hyperlipidemia is associated with endothelial dysfunction, an early event in atherosclerosis and predictor of risk for future coronary artery disease. Epidemiological studies suggest that increased dietary intake of antioxidants reduces the risk of coronary artery disease. The purpose of this study was to determine whether antioxidant vitamin therapy improves endothelial function and affects surrogate biomarkers for oxidative stress and inflammation in hyperlipidemic children. METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled trial, the effects of antioxidant vitamins C (500 mg/d) and E (400 IU/d) for 6 weeks and the National Cholesterol Education Program Step II (NCEP-II) diet for 6 months on endothelium-dependent flow-mediated dilation (FMD) of the brachial artery were examined in 15 children with familial hypercholesterolemia (FH) or the phenotype of familial combined hyperlipidemia (FCH). Antioxidant vitamin therapy improved FMD of the brachial artery compared with baseline (P<0.001) without an effect on biomarkers for oxidative stress (autoantibodies to epitopes of oxidized LDL, F2-isoprostanes, 8-hydroxy-2'-deoxyguanosine), inflammation (C-reactive protein), or levels of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide. CONCLUSIONS: Antioxidant therapy with vitamins C and E restores endothelial function in hyperlipidemic children. Early detection and treatment of endothelial dysfunction in high-risk children may retard the progression of atherosclerosis.

Effect of docosahexaenoic acid on lipoprotein subclasses in hyperlipidemic children (the EARLY study).

To test the hypothesis that a dietary omega-3 fatty acid, docosahexaenoic acid, improves the lipoprotein subclass profile of children who have hyperlipidemia, we conducted a randomized, double-blind, placebo-controlled study. Children who had hyperlipidemia (n = 20) were stabilized on a low-fat diet for 6 weeks and then randomized to receive 1.2 g/day of docosahexaenoic acid for 6 weeks or placebo. Supplementation with docosahexaenoic acid significantly increased low-density lipoprotein subclass 1 and high-density lipoprotein subclass 2 (large and buoyant; less atherogenic particles) by 91% and 14%, respectively, compared with the placebo phase. Low-density lipoprotein subclass 3 (small and dense; more atherogenic particles) decreased by 48%.

Genetic determinants of arterial stiffness.

Stiffness of large arteries (called arteriosclerosis) is an independent predictor of cardiovascular morbidity and mortality. Although previous studies have shown that arterial stiffness is moderately heritable, genetic factors contributing to arterial stiffness are largely unknown. In this paper, we reviewed the available literature on genetic variants that are potentially related to arterial stiffness. Most variants have shown mixed depictions of their association with arterial stiffness across multiple studies. Various methods to measure arterial stiffness at different arterial sites can contribute to these inconsistent results. In addition, studies in patient populations with hypertension or atherosclerosis may overestimate the impact of genetic variants on arterial stiffness. Future studies are recommended to standardize current measures of arterial stiffness in different age groups. Studies conducted in normal healthy subjects may also provide better opportunities to find novel genetic variants of arterial stiffness.

Effects of docosahexaenoic acid on vascular pathology and reactivity in hypertension.

Previous studies have shown that docosahexaenoic acid (DHA) has an antihypertensive effect in spontaneously hypertensive rats (SHR). To investigate possible mechanisms for this effect, vascular pathology and reactivity were determined in SHR treated with dietary DHA. SHR (7 weeks) were fed a purified diet with either a combination of corn/soybean oils or a DHA-enriched oil for 6 weeks. Histological evaluation of heart tissue, aorta, coronary, and renal arteries was performed. Vascular responses were determined in isolated aortic rings. Contractile responses to agonists, including norepinephrine (10(-9) to 10(-4) M), potassium chloride (5-55 mM), and angiotensin II (5 x 10(-7) M) were assessed. Vasorelaxant responses to acetylcholine (10(-9) to 10 (-4) M), sodium nitroprusside (10(-9) to 10(-6) M), papaverine (10(-5) to 10(-4) M), and methoxyverapamil (D600, 1-100 microM) were determined. DHA-fed SHR had significantly reduced blood pressure (P < 0.001) and vascular wall thicknesses in the coronary, thoracic, and abdominal aorta compared with controls (P < 0.05) Contractile responses to agonists mediated by receptor stimulation and potassium depolarization were not altered in DHA-fed SHR. Endothelial-dependent relaxations to acetylcholine were not altered which suggests endothelial-derived nitric oxide production/release is not affected by dietary DHA. Other mechanisms of vascular relaxation, including intracellular cyclic nucleotides, cGMP, and cAMP were not altered by dietary DHA because aortic relaxant responses to sodium nitroprusside and papaverine were similar in control and DHA-fed SHR. No significant differences were seen in relaxant responses to the calcium channel blocker, D600, or contractile responses to norepinephrine in the absence of extracellular calcium. These results suggest that dietary DHA does not affect mechanisms related to extracellular calcium channels or intracellular calcium mobilization. Moreover, the contractile and vasorelaxant responses are not differentially altered with dietary DHA in this in vivo SHR model. The findings demonstrate that dietary DHA reduces systolic blood pressure and vascular wall thickness in SHR. This may contribute to decrease arterial stiffness and pulse pressure, in addition to the antihypertensive properties of DHA. The antihypertensive properties of DHA are not related to alterations in vascular responses.

Familial hypercholesterolemia: genetic predisposition to atherosclerosis.

Familial hypercholesterolemia is one of the most frequent genetic disorders. The increased cholesterol levels in the plasma low-density lipoprotein fraction due to the diminished number or absence of LDL receptors predispose affected individuals to premature atherosclerosis and cardiovascular disease.

IL-17A produced by αß T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction.

Emerging evidence suggests that the T helper 17 (T(H)17) subset of αß T cells contributes to the development of allergic asthma. In this study, we found that mice lacking the αvß8 integrin on dendritic cells did not generate T(H)17 cells in the lung and were protected from airway hyper-responsiveness in response to house dust mite and ovalbumin sensitization and challenge. Because loss of T(H)17 cells inhibited airway narrowing without any obvious effects on airway inflammation or epithelial morphology, we examined the direct effects of T(H)17 cytokines on mouse and human airway smooth muscle function. Interleukin-17A (IL-17A), but not IL-17F or IL-22, enhanced contractile force generation of airway smooth muscle through an IL-17 receptor A (IL-17RA)-IL-17RC, nuclear factor κ light-chain enhancer of activated B cells (NF-κB)-ras homolog gene family, member A (RhoA)-Rho-associated coiled-coil containing protein kinase 2 (ROCK2) signaling cascade. Mice lacking integrin αvß8 on dendritic cells showed impaired activation of this pathway after ovalbumin sensitization and challenge, and the diminished contraction of the tracheal rings in these mice was reversed by IL-17A. These data indicate that the IL-17A produced by T(H)17 cells contributes to allergen-induced airway hyper-responsiveness through direct effects on airway smooth muscle.

Nutrigenomics in cardiovascular disease: implications for the future.

Cardiovascular disease (CVD), the leading cause of morbidity and mortality worldwide, is a complex multifactorial disease which is influenced by environmental and genetic factors. There is substantial evidence on the relationship between diet and CVD risk. An understanding of how genetic variation interacts with the diet to influence CVD risk is a rapidly evolving area of research. Since diet is the mainstay of risk factor modification, it is important to consider potential genetic influences on CVD risk. Nutrigenomics is the study of the interaction between diet and an individual's genetic makeup. Single nucleotide polymorphisms are the key factors in human genetic variation and provide a molecular basis for phenotypic differences between individuals. Whole genome and candidate gene association studies are two main approaches used in cardiovascular genetics to identify disease-causing genes. Recent nutrigenomics studies show the influence of genotype on the responsiveness to dietary factors or nutrients that may reduce CVD risk. Nutrigenomics research is expected to provide the scientific evidence for genotype-based personalized nutrition to promote health and prevent chronic disease, including CVD. It is imperative that healthcare providers, including cardiovascular nurses, are trained in genetics to foster delivery of competent genetic- and genomic-focused care and to facilitate incorporation of this new knowledge into current clinical practice, education, and research.