Update on Omega-3 Polyunsaturated Fatty Acids on Cardiovascular Health.

Twenty percent of deaths in the United States are secondary to cardiovascular diseases (CVD). In patients with hyperlipidemia and hypertriglyceridemia, studies have shown high atherosclerotic CVD (ASCVD) event rates despite the use of statins. Given the association of high triglyceride (TG) levels with elevated cholesterol and low levels of high-density lipoprotein cholesterol, the American Heart Association (AHA)/American College of Cardiology (ACC) cholesterol guidelines recommend using elevated TGs as a "risk-enhancing factor" for ASCVD and using omega 3 fatty acids (Ω3FAs) for patients with persistently elevated severe hypertriglyceridemia. Ω3FA, or fish oils (FOs), have been shown to reduce very high TG levels, hospitalizations, and CVD mortality in randomized controlled trials (RCTs). We have published the largest meta-analysis to date demonstrating significant effects on several CVD outcomes, especially fatal myocardial infarctions (MIs) and total MIs. Despite the most intensive research on Ω3FAs on CVD, their benefits have been demonstrated to cluster across multiple systems and pathologies, including autoimmune diseases, infectious diseases, chronic kidney disease, central nervous system diseases, and, most recently, the COVID-19 pandemic. A review and summary of the controversies surrounding Ω3FAs, some of the latest evidence-based findings, and the current and most updated recommendations on Ω3FAs are presented in this paper.

PET Stress Testing with Coronary Flow Capacity in the Evaluation of Patients with Coronary Artery Disease and Left Ventricular Dysfunction: Rethinking the Current Paradigm.

PURPOSE OF REVIEW: Cardiomyopathy with underlying left ventricular (LV) dysfunction is a heterogenous group of disorders that may be present with, and/or secondary to, coronary artery disease (CAD). The purpose of this review is to demonstrate, via case illustrations, the benefits offered by cardiac positron-emission tomography (PET) stress testing with coronary flow capacity (CFC) in the evaluation and treatment of patients with left ventricular (LV) dysfunction and CAD. RECENT FINDINGS: CFC, a metric that is increasing in prominence, represents the integration of several absolute perfusion metrics into clinical strata of CAD severity. Our prior work has demonstrated improvement in regional perfusion metrics as a result of revascularization to territories with severe reduction in CFC. Conversely, when CFC is adequate, there is no change in regional perfusion metrics following revascularization, despite angiographically severe stenosis. Furthermore, Gould et al. demonstrated decreased rates of myocardial infarction and death following revascularization of myocardium with severely reduced CFC, with no clinical benefit observed following revascularization of patients with preserved CFC. In a series of cases, we present pre-revascularization and post-revascularization PET scans with perfusion metrics in patients with LV dysfunction and CAD. In these examples, we demonstrate improvement in LV function and perfusion metrics following revascularization only in cases where baseline CFC is severely reduced. PET with CFC offers unique guidance regarding revascularization in patients with reduced LV function and CAD.

An Update on Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health.

Interest in the potential cardiovascular (CV) benefits of omega-3 polyunsaturated fatty acids (Ω-3) began in the 1940s and was amplified by a subsequent landmark trial showing reduced CV disease (CVD) risk following acute myocardial infarction. Since that time, however, much controversy has circulated due to discordant results among several studies and even meta-analyses. Then, in 2018, three more large, randomized trials were released-these too with discordant findings regarding the overall benefits of Ω-3 therapy. Interestingly, the trial that used a higher dose (4 g/day highly purified eicosapentaenoic acid (EPA)) found a remarkable, statistically significant reduction in CVD events. It was proposed that insufficient Ω-3 dosing (<1 g/day EPA and docosahexaenoic acid (DHA)), as well as patients aggressively treated with multiple other effective medical therapies, may explain the conflicting results of Ω-3 therapy in controlled trials. We have thus reviewed the current evidence regarding Ω-3 and CV health, put forth potential reasoning for discrepant results in the literature, highlighted critical concepts such as measuring blood levels of Ω-3 with a dedicated Ω-3 index and addressed current recommendations as suggested by health care professional societies and recent significant scientific data.

Effect of Omega-3 Dosage on Cardiovascular Outcomes: An Updated Meta-Analysis and Meta-Regression of Interventional Trials.

OBJECTIVES: To quantify the effect of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on cardiovascular disease (CVD) prevention and the effect of dosage. METHODS: This study is designed as a random effects meta-analysis and meta-regression of randomized control trials with EPA/DHA supplementation. This is an update and expanded analysis of a previously published meta-analysis which covers all randomized control trials with EPA/DHA interventions and cardiovascular outcomes published before August 2019. The outcomes included are myocardial infarction (MI), coronary heart disease (CHD) events, CVD events (a composite of MI, angina, stroke, heart failure, peripheral arterial disease, sudden death, and non-scheduled cardiovascular surgical interventions), CHD mortality and fatal MI. The strength of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation framework. RESULTS: A total of 40 studies with a combined 135,267 participants were included. Supplementation was associated with reduced risk of MI (relative risk [RR], 0.87; 95% CI, 0.80 to 0.96), high certainty number needed to treat (NNT) of 272; CHD events (RR, 0.90; 95% CI, 0.84 to 0.97), high certainty NNT of 192; fatal MI (RR, 0.65; 95% CI, 0.46 to 0.91]), moderate certainty NNT = 128; and CHD mortality (RR, 0.91; 95% CI, 0.85 to 0.98), low certainty NNT = 431, but not CVD events (RR, 0.95; 95% CI, 0.90 to 1.00). The effect is dose dependent for CVD events and MI. CONCLUSION: Cardiovascular disease remains the leading cause of death worldwide. Supplementation with EPA and DHA is an effective lifestyle strategy for CVD prevention, and the protective effect probably increases with dosage.

Sea Change for Marine Omega-3s: Randomized Trials Show Fish Oil Reduces Cardiovascular Events.

Recently, 3 large randomized controlled trials (RCTs) have assessed the effects of supplementation with marine omega-3 fatty acids on the occurrence of cardiovascular disease (CVD) events. We reviewed this evidence and considered it in the context of the large and growing body of data on the CV health effects of marine omega-3s. One RCT examining 8179 patients, most with coronary heart disease (CHD), reported that 4 grams/day of a highly purified omega-3 product containing eicosapentaenoic acid (EPA) reduced the risk for major adverse CV events by 25% (P<.001). Two other recent RCTs in primary prevention populations showed that approximately 1 gram/day of purified fish oil containing 840 mg/day of EPA and docosahexaenoic acid (DHA) significantly reduced risks of CHD and CV death, especially in individuals who did not consume fish and seafood frequently. The American Heart Association (AHA) continues to emphasize the importance of marine omega-3s as a nutrient for potentially reducing risks of congestive heart failure, CHD, ischemic stroke, and sudden cardiac death. Marine omega-3s should be used in high doses for patients with CHD on statins who have elevated triglycerides and at about 1 gram/day for primary prevention for individuals who do not consume at least 1.5 fish or seafood meals per week.

The Role of Technology in Chronic Disease Care.

Chronic disease represents the epidemic of our time, present in half the adult population and responsible for 86% of United States (US) healthcare costs and 70% of deaths. The major chronic diseases are primarily due to health risk behaviors that are widely communicable across populations. As a nation, the US has performed poorly in managing chronic disease, in large part because of a failed delivery model of care. New opportunities exist as a result of recent advances in home-based wireless devices, apps and wearables, enabling health delivery systems to monitor disease metrics in near real time. These technologies provide a framework for patient engagement and a new model of care delivery utilizing integrated practice units, both of which are needed to navigate the healthcare needs of the 21st century.

Health care 2020: reengineering health care delivery to combat chronic disease.

Chronic disease has become the great epidemic of our times, responsible for 75% of total health care costs and the majority of deaths in the US. Our current delivery model is poorly constructed to manage chronic disease, as evidenced by low adherence to quality indicators and poor control of treatable conditions. New technologies have emerged that can engage patients and offer additional modalities in the treatment of chronic disease. Modifying our delivery model to include team-based care in concert with patient-centered technologies offers great promise in managing the chronic disease epidemic.

Omega-3 fatty acids: a growing ocean of choices.

There has been increasing interest in the health benefits of supplemental and/or dietary omega-3 polyunsaturated fatty acids (PUFAs), particularly in their role in disease prevention. This interest escalated once their effects on cardiovascular health were observed from numerous observational studies in populations whose diet consisted mainly of fish. Research has since been undertaken on omega-3 PUFAs to investigate their health benefits in a vast array of medical conditions, including primary and secondary prevention. This article discusses the evidence and controversies concerning omega-3 PUFAs in various health conditions. In addition to the effects on cardiovascular health, omega-3 PUFAs have been shown to prevent the development of dementia, reduce systemic inflammatory diseases, prevent prostate cancer, and possibly have a role in the treatment of depression and bipolar disorder.

Atrial fibrillation in the 21st century: a current understanding of risk factors and primary prevention strategies.

Atrial fibrillation (AF) is the most common arrhythmia worldwide, and it has a significant effect on morbidity and mortality. It is a significant risk factor for stroke and peripheral embolization, and it has an effect on cardiac function. Despite widespread interest and extensive research on this topic, our understanding of the etiology and pathogenesis of this disease process is still incomplete. As a result, there are no set primary preventive strategies in place apart from general cardiology risk factor prevention goals. It seems intuitive that a better understanding of the risk factors for AF would better prepare medical professionals to initially prevent or subsequently treat these patients. In this article, we discuss widely established risk factors for AF and explore newer risk factors currently being investigated that may have implications in the primary prevention of AF. For this review, we conducted a search of PubMed and used the following search terms (or a combination of terms): atrial fibrillation, metabolic syndrome, obesity, dyslipidemia, hypertension, type 2 diabetes mellitus, omega-3 fatty acids, vitamin D, exercise toxicity, alcohol abuse, and treatment. We also used additional articles that were identified from the bibliographies of the retrieved articles to examine the published evidence for the risk factors of AF.

Vitamin D and cardiovascular disease will it live up to its hype?

Substantial evidence suggests that a large portion of the population have suboptimal levels of vitamin D, which may adversely affect the cardiovascular (CV) system, including increasing levels of parathyroid hormone, activating the renin-angiotensin-aldosterone system, and increasing insulin resistance, thus leading to hypertension and left ventricular hypertrophy, metabolic syndrome/diabetes mellitus, systemic inflammation, and increased risk of atherosclerosis and CV disease events. We review the evidence that vitamin D deficiency is associated with incident CV disease events, as well as evidence that vitamin D supplementation is associated with reduction in CV diseases. Although the current evidence has created substantial hype, randomized controlled trials are needed to determine whether routine vitamin D assessment and supplementation will improve CV outcomes.

Omega-3 polyunsaturated fatty acids and cardiovascular diseases.

Omega-3 polyunsaturated fatty acid (omega-3 PUFA) therapy continues to show great promise in primary and, particularly in secondary prevention of cardiovascular (CV) diseases. The most compelling evidence for CV benefits of omega-3 PUFA comes from 4 controlled trials of nearly 40,000 participants randomized to receive eicosapentaenoic acid (EPA) with or without docosahexaenoic acid (DHA) in studies of patients in primary prevention, after myocardial infarction, and most recently, with heart failure (HF). We discuss the evidence from retrospective epidemiologic studies and from large randomized controlled trials showing the benefits of omega-3 PUFA, specifically EPA and DHA, in primary and secondary CV prevention and provide insight into potential mechanisms of these observed benefits. The target EPA + DHA consumption should be at least 500 mg/day for individuals without underlying overt CV disease and at least 800 to 1,000 mg/day for individuals with known coronary heart disease and HF. Further studies are needed to determine optimal dosing and the relative ratio of DHA and EPA omega-3 PUFA that provides maximal cardioprotection in those at risk of CV disease as well in the treatment of atherosclerotic, arrhythmic, and primary myocardial disorders.

New data on the clinical impact of exercise training, fish oils, and statins in heart failure.

Despite major advances in the field of cardiovascular (CV) diseases, heart failure (HF) continues to result in considerable CV morbidity and mortality and accounts for an increasing number of acute hospitalizations in adult patients. Recent major trials have focused on exercise training programs and the widely available nutraceutical omega-3 polyunsaturated fatty acids or fish oil and statins in patients with HF. In this article, we provide insight into the interpretation of the evidence base for these distinct interventions in HF and provide guidance for the clinical incorporation of exercise training and fish oil therapy for additional CV protection in chronic HF.

The role of fish oil in arrhythmia prevention.

Numerous epidemiological studies, case-control series, and randomized trials have demonstrated the ability of fish oil to reduce major cardiovascular events, particularly sudden cardiac death and all-cause mortality. We discuss the potential benefits of fish oil therapy to improve overall autonomic tone and potentially reduce the risk of major ventricular and atrial arrhythmias. Specifically, this review focuses on how fish oil therapy has performed in 3 primary prevention trials in patients with implantable cardioverter defibrillators, reviews the effects that fish oil has on the autonomic nervous system, focuses on the use of fish oil as a novel therapy for atrial fibrillation, and revisits other beneficial properties of fish oil (ie, ability to lower serum triglycerides, anti-inflammatory effects, and possible improvements in arterial pressure/diastolic function). We also discuss the safety profile of fish oil, including effects on bleeding time and bleeding complications as well as provide commentary regarding fish oil supplementation in light of increasing contaminants contained in fish. In summary, any patient with documented coronary heart disease and those with risk factors for sudden cardiac death, such as left ventricular dysfunction, left ventricular hypertrophy, prior myocardial infarction, or high-grade ventricular dysrhythmias, should consider fish oil supplementation. The American Heart Association recommends four 3-ounce servings of oily fish weekly. For those who cannot eat fish or do not have access to fish, as well as those who would prefer not to eat fish regularly, capsules of fish oil are readily available in various concentrations. At the present time, we recommend doses of eicosapentanoic acid and docosahexanoic acid in the combined range of 800 to 1000 mg/day for primary and secondary prevention of cardiovascular disease.

Efficacy and safety of intensive statin therapy in the elderly.

Numerous epidemiologic and intervention trials, including many studying elderly cohorts, have demonstrated the importance of lipids in primary and secondary preventions of cardiovascular diseases, including coronary heart disease (CHD) and stroke. More recent studies have demonstrated that more intensive statin therapy that reduces low-density lipoprotein cholesterol levels to <70 to 80 mg/dL have resulted in more marked cardiovascular event reduction than less intensive statin treatment. The authors review the efficacy and safety of intensive vs less intensive statin therapy. Specifically, 4 such studies with sufficient data in elderly patients, including 2 trials of patients with stable CHD and 2 with acute coronary syndrome, demonstrating the efficacy and safety of intensive statin therapy with high-dose (80 mg) atorvastatin are reviewed in detail. Although elderly patients may be more susceptible to drug interactions when receiving high doses of statins, the present evidence supports the use of intensive statin therapy in most high-risk elderly patients both with stable CHD and following acute coronary syndrome.

Fish oils produce anti-inflammatory effects and improve body weight in severe heart failure.

BACKGROUND: Fish oils have been shown to reduce production of tumor necrosis factor-alpha (TNF-alpha) in healthy subjects. We sought to evaluate the effects of fish oils on pro-inflammatory cytokines and body weight in patients with advanced heart failure. METHODS: Fourteen patients (New York Heart Association [NYHA] Class III to IV heart failure) were randomized in a double-blinded trial to active therapy with 8 g of n-3 fatty acids (Group A, n = 7) or placebo (Group B, n = 7) for 18 weeks. TNF-alpha and interleukin-1 (IL-1) production were measured by radioimmunoassay after endotoxin stimulation of peripheral blood mononuclear cells. RESULTS: Placebo-treated patients had a 44% increase in TNF-alpha (from 1.28 to 1.84 pg/ml; p = 0.07) but no significant change in IL-1 (from 0.68 to 0.78 pg/ml) production. n-3 fatty acids resulted in a 59% reduction in TNF-alpha (from 1.64 to 0.68 pg/ml; p = 0.02) and 39% decrease in IL-1 (from 1.98 to 1.21 pg/ml; p = 0.09) production. There was an inverse correlation between change in TNF-alpha production and change in percent body fat (r = -0.6; p = 0.02). CONCLUSIONS: Fish oils decrease TNF-alpha production in heart failure and improve body weight. Fish oil therapy may represent a novel therapeutic approach in late-stage heart failure characterized by cardiac cachexia.

Importance and management of dyslipidemia in the metabolic syndrome.

The metabolic syndrome is a common disorder characterized by central obesity, impaired glucose tolerance, hypertension, and atherogenic dyslipidemia (including the combination of hypertriglyceridemia, low levels of high-density lipoprotein cholesterol, and a preponderance of small, dense low-density lipoprotein particles). In this manuscript, we review the pathogenesis and significance of dyslipidemia in the metabolic syndrome, the role of nonpharmacologic therapy with therapeutic lifestyle changes, and drug therapies, including statins, fibrates, nicotinic acid, and omega-3 fatty acids or fish oils, alone or in drug combinations, to improve lipids and reduce the chance of subsequent cardiovascular disease events.

Relation between left ventricular geometry and transmural dispersion of repolarization.

Studies have shown an association between left ventricular (LV) geometry and complex ventricular ectopic activity. Increased transmural dispersion of repolarization (TDR), which correlates to the interval from the peak to the end of the T wave (Tpe) on the surface electrocardiogram, is linked to ventricular tachyarrhythmias. The relation between LV geometry and TDR is unknown. The mean Tpe interval, measured from leads V(1) to V(3) of the surface electrocardiogram, was assessed in 300 patients (50% men) who had normal LV systolic function and QRS duration and were categorized into 3 equal groups, which were matched by age and gender, according to echocardiographically determined LV geometry (normal structure, concentric remodeling, and LV hypertrophy). The Tpe interval was corrected for the QT interval using Tpe/QTc and was compared among the 3 groups. Compared with those who had normal LV structure, the Tpe interval was significantly prolonged in those who had LV hypertrophy and significantly shortened in those who had concentric remodeling (p = <0.0001 for the 2 comparisons). Correcting for the QT interval using Tpe/QTc yielded similar results. Thus, TDR was increased in patients who had LV hypertrophy but decreased in concentric remodeling compared with those who had normal cardiac structure. Although LV hypertrophy represents a maladaptive geometric process that results in an unfavorable electrical substrate, concentric remodeling may represent a structural adaptation that has a more favorable electrical milieu.