Omega-3 fatty acids in primary and secondary prevention of cardiovascular diseases.

Even with substantial progress in primary and secondary prevention, cardiovascular disease (CVD) persists as a major cause of mortality and morbidity globally. Omega-3 polyunsaturated fatty acids (Ω-3 PUFAs) have gained considerable attention for their ability to improve CV health and prognosis. Metanalyses of randomized controlled trials have demonstrated Ω-3 PUFAs' positive impact on CVD outcomes for both primary and secondary prevention endpoints. Marine Ω-3 PUFAs also improve CVD risk factors including blood pressure, lipids, and inflammation; however, many physicians do not recommend Ω-3 PUFAs, largely due to inconsistent results in randomized trials. In this comprehensive review article, we evaluate both historic and current data concerning primary and secondary prevention of CVD with use of Ω-3 PUFAs, delve into the potential causes for the varied results, and examine the most current recommendations on the usage of Ω-3 PUFAs.

Estrogen and cardiovascular disease.

A large body of scientific research accumulated over the past twenty years documents the cardiovascular (CV) benefits of estradiol (E2) and progesterone (P4) in reproductive aged women. In contrast, accelerated development of CV disease (CVD) occurs in the absence of ovarian produced E2 and P4. Hormone replacement therapy (HRT) with E2 and P4 has been shown to cause no harm to younger menopausal women. This robust scientific data supports a reconsideration of the prescriptive use of E2 and P4 as preventative therapeutics for the reduction of CVD, even without additional large-scale studies of the magnitude of the Women's Health Initiative (WHI). With the current expanded understanding of the critical modulatory role played by E2 on a multitude of systems and enzymes impacting CVD onset, initiation of HRT shortly after cessation of ovarian function, known as the "Timing Hypothesis", should be considered to delay CVD in recently postmenopausal women.

Imaging of left ventricular outflow tract obstruction in hypertrophic cardiomyopathy.

PURPOSE OF REVIEW: The current article reviews obstructive forms of hypertrophic cardiomyopathy and associated morphologic cardiac abnormalities. It focuses on echocardiographic imaging of the left ventricular (LV) outflow tract obstruction, its evaluation, prognostication, and differentiation from other conditions mimicking obstructive hypertrophic cardiomyopathy. RECENT FINDINGS: Symptomatic patients with LV outflow tract (LVOT) gradients at least 50 mmHg on maximally tolerated medical therapy are candidates for advanced therapies. Resting echocardiography may only identify 30% of patients with obstructive physiology. Provocative maneuvers are essential for symptomatic patients with hypertrophic cardiomyopathy (HCM). Exercise echocardiography is recommended if they fail to provoke a gradient. Although dynamic LV tract obstruction is seen with obstructive HCM, it is not specific to this condition and exists in other physiologic and pathophysiologic states. Careful clinical evaluation and imaging techniques aid in the differentiation of HCM from these conditions. SUMMARY: Imaging plays an integral role in the diagnosis, prognosis, and risk stratification of HCM patients. Newer imaging technologies, including 3D transthoracic echocardiography, 3D transesophageal, speckle-derived 2D strain, and cardiac MRI, allow for a better hemodynamic understanding of systolic anterior motion and LV tract obstruction. Evolving techniques, that is, artificial intelligence, will undoubtedly further increase diagnostic capabilities. Newer medical therapies are available with the hope that this will lead to better patient management.

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.

The Impact of Obesity in Heart Failure.

Overweight and obesity adversely impact cardiac structure and function, affecting systolic and diastolic ventricular function. Epidemiologic studies have documented an obesity paradox in large heart failure cohorts, where overweight and obese individuals with established heart failure have a better short- and medium-term prognosis compared with leaner patients; this relationship is strongly impacted by level of cardiorespiratory fitness. There are implications for therapies aimed at increasing lean mass as well as weight loss and improvements in quality of diet for the prevention and treatment of heart failure and concomitant obesity to improve cardiorespiratory fitness.

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.

Implications of obesity across the heart failure continuum.

The obesity paradox, which suggests a survival advantage for the obese in heart failure (HF) has sparked debate in the medical community. Studies demonstrate a survival advantage in obese patients with HF, including those with advanced HF requiring continuous inotropic support for palliation or disease modifying therapy with a left ventricular assist device (LVAD) or heart transplantation (HT). Importantly, the obesity paradox is affected by the level of cardiorespiratory fitness (CRF). It is now recommended that HF patients with body mass index ≥35 kg/m2 achieve at least 5-10% weight loss, in order to improve symptoms and cardiac function, though more robust data are urgently needed. CRF may be the single best predictor of overall health and small improvements in fitness levels may lead to improved outcomes in HF. In addition to implications of obesity in chronic HF, we also discuss management of obese patients with advanced HF and their implications for therapies such as LVAD implantation and HT.

A Review of Obesity, Physical Activity, and Cardiovascular Disease.

PURPOSE OF REVIEW: The focus of this review is to discuss obesity, physical activity (and physical inactivity/sedentary behavior), cardiovascular disease (CVD), and their often interrelated health implications. The authors summarize the pathophysiological changes associated with obesity, which lead to the development of CVD, recommendations for interventions such as diet, increased physical activity, and weight loss according to current literature and guidelines, and the critical importance of cardiorespiratory fitness (CRF). RECENT FINDINGS: Clinical trials continue to demonstrate improved outcomes among overweight or obese individuals who achieve a healthy weight using various methods. Increasing CRF levels appears to demonstrate the largest health improvements, regardless of underlying comorbidities or achieving weight loss. CRF, which is perhaps the single most important predictor of overall health, seems more important than weight loss alone regarding improved CVD outcomes in the obese population. These findings are reproduced in studies involving patients with various forms of CVD and CVD risk factors. The importance of CRF is well established; future endeavors to establish specific CRF targets for various patient cohorts are needed.

The Impact of Obesity in Heart Failure.

Obesity has reached worldwide epidemic proportions, adversely impacting health on a global scale. Overweight and obesity adversely impact cardiac structure and function, affecting systolic and diastolic ventricular function. Studies and meta-analyses have documented an obesity paradox in large heart failure cohorts, where overweight and obese individuals with established heart failure have a better short- and medium-term prognosis compared with lean patients; this relationship is strongly impacted by level of cardiorespiratory fitness. There are implications for therapies aimed at increasing lean and muscle mass, and weight loss, for the prevention and treatment of compared with in patients with concomitant obesity.

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.

Effects of Physical Activity, Exercise, and Fitness on Obesity-Related Morbidity and Mortality.

Obesity is associated with increased prevalence of cardiovascular (CV) disease (CVD) risk factors, which may adversely impact CV structure and function and may increase the prevalence of most CVD, particularly heart failure (HF) and coronary heart disease (CHD). Physical activity (PA), exercise training (ET) and cardiorespiratory fitness (CRF) are all associated with marked reductions in most CVD, including HF and CHD. Additionally, PA/ET and, especially CRF, markedly alter the relationship between adiposity and subsequent major CVD outcomes and dramatically impact the "obesity paradox," which are all reviewed, including attention to the debate regarding "fitness versus fatness" for long-term prognosis, including in patients with established CVD.

Obesity paradox in cardiovascular disease: where do we stand?

Obesity is associated with an increased risk of developing cardiovascular disease (CVD), particularly heart failure (HF) and coronary heart disease (CHD). The mechanisms through which obesity increases CVD risk involve changes in body composition that can affect hemodynamics and alters heart structure. Pro-inflammatory cytokines produced by the adipose tissue itself which can induce cardiac dysfunction and can promote the formation of atherosclerotic plaques. When obesity and HF or CHD coexist, individuals with class I obesity present a more favorable prognosis compared to individuals who are normal or underweight. This phenomenon has been termed the "obesity paradox." Obesity is defined as an excess fat mass (FM), but individuals with obesity typically also present with an increased amount of lean mass (LM). The increase in LM may explain part of the obesity paradox as it is associated with improved cardiorespiratory fitness (CRF), a major determinant of clinical outcomes in the general population, but particularly in those with CVD, including HF. While increased LM is a stronger prognosticator in HF compared to FM, in patients with CHD excess FM can exert protective effects particularly when not associated with increased systemic inflammation. In the present review, we discuss the mechanisms through which obesity may increase the risk for CVD, and how it may exert protective effects in the setting of established CVD, with a focus on body composition. We also highlight the importance of measuring or estimating CRF, including body composition-adjusted measures of CRF (ie, lean peak oxygen consumption) for an improved risk status stratification in patients with CVD and finally, we discuss the potential non-pharmacologic therapeutics, such as exercise training and dietary interventions, aimed at improving CRF and perhaps clinical outcomes.