Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies.

BACKGROUND: The effect of marine omega-3 PUFAs on risk of stroke remains unclear. METHODS: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome. RESULTS: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76-0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74-0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81-0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78-0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD. CONCLUSIONS: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.

Training Strategies to Optimize Cardiovascular Durability and Life Expectancy.

The optimal dose of physical activity and best types of exercise for improving cardiovascular (CV) durability and optimizing longevity are unknown. The purpose of this article is to review the recent literature on the effects of duration and intensity of exercise, physical fitness, and specific types of training/sports on long-term CV health and life expectancy. A systematic review of recent studies (2011 to 2022) was conducted using PubMed. Studies were included if they addressed the topic of fitness and/or exercise dose/type and CV health and/or life expectancy. Epidemiological studies show that cardiorespiratory fitness (is inversely related to risk of all-cause mortality, with no increased mortality risk in the most fit cohort. Being unfit is among most potent risk factors for all-cause mortality. Moderate PA (MPA) and vigorous PA (VPA) were associated with reduced CV and all-cause mortality in a recent definitive study. Paradoxically, high doses of MPA reduced both CV and all-cause mortality better than did high doses of VPA. A large meta-analysis showed that strength training was independently associated with lower rates of all-cause mortality and CV disease, though the best outcomes were associated with a cumulative dose of about 60 minutes/week. Physical interactive play is strongly associated with improved life expectancy. Physical fitness is a key determinant of CV health and life expectancy. Moderate to vigorous exercise, strength training and interactive sports are associated with improved life expectancy. Very large volumes of strenuous exercise and/or weightlifting may not be the ideal for optimizing longevity.

Nutraceutical Prevention of Diabetic Complications-Focus on Dicarbonyl and Oxidative Stress.

Oxidative and dicarbonyl stress, driven by excess accumulation of glycolytic intermediates in cells that are highly permeable to glucose in the absence of effective insulin activity, appear to be the chief mediators of the complications of diabetes. The most pathogenically significant dicarbonyl stress reflects spontaneous dephosphorylation of glycolytic triose phosphates, giving rise to highly reactive methylglyoxal. This compound can be converted to harmless lactate by the sequential activity of glyoxalase I and II, employing glutathione as a catalyst. The transcription of glyoxalase I, rate-limiting for this process, is promoted by Nrf2, which can be activated by nutraceutical phase 2 inducers such as lipoic acid and sulforaphane. In cells exposed to hyperglycemia, glycine somehow up-regulates Nrf2 activity. Zinc can likewise promote glyoxalase I transcription, via activation of the metal-responsive transcription factor (MTF) that binds to the glyoxalase promoter. Induction of glyoxalase I and metallothionein may explain the protective impact of zinc in rodent models of diabetic complications. With respect to the contribution of oxidative stress to diabetic complications, promoters of mitophagy and mitochondrial biogenesis, UCP2 inducers, inhibitors of NAPDH oxidase, recouplers of eNOS, glutathione precursors, membrane oxidant scavengers, Nrf2 activators, and correction of diabetic thiamine deficiency should help to quell this.

Monounsaturated Fat vs Saturated Fat: Effects on Cardio-Metabolic Health and Obesity.

For over 40 years saturated fat, the fat found primarily in animal foods, was thought to be the main culprit for increasing cholesterol levels and causing heart disease. During this same time vegetable oils were promoted as being heart healthy because they could lower cholesterol. However, recently the evidence implicating saturated fat as being harmful to heart health has been challenged and more studies are beginning to show the harms from consuming industrially produced vegetable oils. Furthermore, monounsaturated fats, found in olives, olive oil, certain nuts and avocadoes have been promoted as being part of a healthy Mediterranean diet. This paper will provide a brief review comparing the effects of saturated fat to monounsaturated fat.

Does Fish Oil Reduce the Risk of Cardiovascular Events and Death? Recent Level 1 Evidence Says Yes: PRO: Fish Oil is Useful to Prevent or Treat Cardiovascular Disease.

Over the past decade there has been a considerable debate whether fish oil supplementation works to prevent and/or treat cardiovascular disease. This is due to the fact that previous studies testing fish oil in Italy and Japan found significant reductions in all-cause mortality, sudden cardiac death, and cardiovascular events, whereas more recent studies have in general been considered negative. We will discuss the reasons for these discrepancies and pave a better path forward when it comes to interpreting studies testing fish oil for the prevention or treatment of cardiovascular disease.

Magnesium and Vitamin D Deficiency as a Potential Cause of Immune Dysfunction, Cytokine Storm and Disseminated Intravascular Coagulation in covid-19 patients.

Magnesium and vitamin D each have the possibility of affecting the immune system and consequently the cytokine storm and coagulation cascade in COVID-19 infections. Vitamin D is important for reducing the risk of upper respiratory tract infections and plays a role in pulmonary epithelial health. While the importance of vitamin D for a healthy immune system has been known for decades, the benefits of magnesium has only recently been elucidated. Indeed, magnesium is important for activating vitamin D and has a protective role against oxidative stress. Magnesium deficiency increases endothelial cell susceptibility to oxidative stress, promotes endothelial dysfunction, reduces fibrinolysis and increases coagulation. Furthermore, magnesium deficient animals and humans have depressed immune responses, which, when supplemented with magnesium, a partial or near full reversal of the immunodeficiency occurs. Moreover, intracellular free magnesium levels in natural killer cells and CD8 killer T cells regulates their cytotoxicity. Considering that magnesium and vitamin D are important for immune function and cellular resilience, a deficiency in either may contribute to cytokine storm in the novel coronavirus 2019 (COVID-19) infection.

Technetium pyrophosphate nuclear scintigraphy for cardiac amyloidosis: Imaging at 1 vs 3 hours and planar vs SPECT/CT.

BACKGROUND: Multi-societal consensus recommendations endorse both planar and single photon emission tomographic (SPECT) image acquisitions for the evaluation of cardiac amyloidosis. However, the correlation between planar and SPECT findings and the optimal timing of image acquisitions remain uncertain. METHODS: This is an analysis of 109 consecutive patients who underwent technetium pyrophosphate nuclear scintigraphy for the evaluation of cardiac amyloidosis. Patients were imaged at 1 and 3 hours after radiotracer injection using both planar and SPECT/CT, and the correlations between imaging protocols were compared. RESULTS: In the overall cohort (median age 77 years, 75% male), 33 patients had radiotracer localized to the myocardium on SPECT/CT images. There was strong correlation between 1- and 3-hour planar heart-to-contralateral lung ratios (mean difference 0.07, r = 0.94). However, there was discordance between planar image interpretation (based upon semiquantitative score and H/CL ratio) and myocardial localization of radiotracer on SPECT/CT in 17 patients (16%). The pattern of SPECT/CT uptake was identical at 1 and 3 hours in all cases (32 diffuse, 1 focal). CONCLUSION: These data support the recommendation that SPECT/CT should be obtained in addition to planar images when performing nuclear scintigraphy for the detection of cardiac amyloidosis. A 1-hour planar and SPECT/CT protocol appears optimal.

The Benefits of Omega-3 Fats for Stabilizing and Remodeling Atherosclerosis.

The majority of acute coronary syndromes are caused by the rupture of plaques rendered vulnerable by oxidized lipids, inflammation, and a thin fibrous cap with reduced collagen and smooth muscle cell content.2 Thus, stabilizing and reversing vulnerable atherosclerotic plaques can help to prevent cardiovascular events. In this regard, long-chain omega-3 fatty acids have a plethora of data for stabilizing vulnerable atherosclerotic plaques as well as reversing atherosclerosis. This review paper will summarize the observational data as well as animal and human studies supporting such a role and further discuss the current controversies around omega-3 supplementation.

Training for Longevity: The Reverse J-Curve for Exercise.

A wealth of scientific literature backs the unique therapeutic benefits of exercise for quality of life, cardiovascular (CV) health, and longevity. Consequently, many have assumed that more exercise is always better. However, chronic excessive endurance exercise might adversely impact CV health. Ultra-endurance races can inflict acute myocardial damage, as evidenced by elevations in troponin and brain natriuretic peptide. Moreover, sudden cardiac arrest occurs more often in marathons and triathlons than in shorter races. Veteran endurance athletes often show abnormal cardiac remodeling with increased risk for myocardial fibrosis and coronary calcification. Chronic excessive exercise has been consistently associated with increased risks of atrial fibrillation (AF), and along with some attenuation of longevity benefits. The optimal dose of exercise remains unknown and probably differs among individuals. Current studies suggest that 2.5 to 5 hours/week of moderate or vigorous physical activity will confer maximal benefits; >10 hours/week may reduce these health benefits.

The Benefits of Marine Omega-3s for the Prevention and Treatment of Cardiovascular Disease.

There has been a raging debate whether marine omega-3s are effective for the prevention of cardiovascular disease. Our review paper discusses the landmark clinical studies testing the benefits of marine omega-3s. Moreover, for the first time, the REDUCE-IT study tested a high dose of marine omega-3s (4 grams of icosapent ethyl per day) on top of statin therapy in patients with established cardiovascular disease or with diabetes and additional risk factors with concomitant high triglyceride levels and noted a highly significant 25% reduction in the primary endpoint. Thus, in patients who are not in the early post myocardial infarction setting, high dose marine omega-3s (4 grams per day) may be required to provide cardiovascular benefit when given on top of optimized medical therapy.

Salt and hypertension: what do we know?

PURPOSE OF REVIEW: To evaluate the evidence for population-wide sodium restriction. RECENT FINDINGS: The recommendations for population-wide sodium restriction largely rely on one surrogate marker (blood pressure). However, recent evidence suggests that when looking beyond blood pressure (e.g. heart rate, aldosterone, renin, cholesterol, triglycerides, noradrenaline and adrenaline), the net effect of sodium restriction is likely harmful. Prospective studies support the notion that those consuming the lowest amounts of salt are at the highest risk of cardiovascular events and premature death. SUMMARY: There is no definitive proof that sodium restriction reduces cardiovascular events or death. It is time for the dietary guidelines to look at the totality of the evidence and reconsider the advice around population-wide sodium restriction.

Sugar addiction: is it real? A narrative review.

In animal studies, sugar has been found to produce more symptoms than is required to be considered an addictive substance. Animal data has shown significant overlap between the consumption of added sugars and drug-like effects, including bingeing, craving, tolerance, withdrawal, cross-sensitisation, cross-tolerance, cross-dependence, reward and opioid effects. Sugar addiction seems to be dependence to the natural endogenous opioids that get released upon sugar intake. In both animals and humans, the evidence in the literature shows substantial parallels and overlap between drugs of abuse and sugar, from the standpoint of brain neurochemistry as well as behaviour.

The Goldilocks Zone for Exercise: Not Too Little, Not Too Much.

Homo sapiens are evolutionarily adapted to be very physically active throughout life, and thus habitual physical activity (PA) is essential for well-being and longevity. Never the less, middle-aged and older individuals engaging in excessive strenuous endurance exercise appear to be at increased risk for a variety of adverse cardiovascular (CV) effects including atrial fibrillation, myocardial fibrosis, and coronary atherosclerosis. An emerging body of evidence indicates U-shaped or reverse J-shaped curves whereby low doses and moderate doses of PA significantly reduce long-term risks for both total mortality and CV mortality, however, at very high doses of chronic strenuous exercise much of the protection against early mortality and CV disease is lost. The optimal dose, or what we term 'Goldilocks Zone,' of PA may be: at least 150 minutes per week of moderate-intensity aerobic exercise or 75 minutes per week of vigorous-intensity aerobic activity, but not more than four to five cumulative hours per week of vigorous (heart-pounding, sweatproducing) exercise, especially for those over 45 years of age. It is also important to take at least one day per week off from vigorous exercise. There appears to be no concerns about an upper threshold for safety for leisure-time low-to-moderate intensity activities such as walking at a comfortable pace, housework, gardening, etc. After every 30 consecutive minutes spent sitting, stand up and move, ideally walking briskly for about five minutes.

Not Salt But Sugar As Aetiological In Osteoporosis: A Review.

Salt has notoriously been blamed for causing an increase in the urinary excretion of calcium, and thus is a considered a risk factor for osteoporosis. However, the increase in the urinary excretion of calcium with higher sodium intakes can be offset by the increased intestinal absorption of dietary calcium. Thus, the overall calcium balance does not appear to be reduced with a higher sodium intake. However, the other ubiquitous white crystal, sugar, may lead to osteoporosis by increasing inflammation, hyperinsulinemia, increased renal acid load, reduced calcium intake, and increased urinary calcium excretion. Sugar, not salt, is the more likely white crystal to be a risk factor for osteoporosis when overconsumed.

Exercise and the cardiovascular system: clinical science and cardiovascular outcomes.

Substantial evidence has established the value of high levels of physical activity, exercise training (ET), and overall cardiorespiratory fitness in the prevention and treatment of cardiovascular diseases. This article reviews some basics of exercise physiology and the acute and chronic responses of ET, as well as the effect of physical activity and cardiorespiratory fitness on cardiovascular diseases. This review also surveys data from epidemiological and ET studies in the primary and secondary prevention of cardiovascular diseases, particularly coronary heart disease and heart failure. These data strongly support the routine prescription of ET to all patients and referrals for patients with cardiovascular diseases, especially coronary heart disease and heart failure, to specific cardiac rehabilitation and ET programs.

Good Fats versus Bad Fats: A Comparison of Fatty Acids in the Promotion of Insulin Resistance, Inflammation, and Obesity.

Recently, debate has erupted in both the scientific community and throughout the lay public around whether a low-fat or low-carbohydrate diet is better for weight loss. In other words, is it better to cut fat or cut carbohydrate for weight loss. However, going beyond this debate (fat versus carbohydrate), are questions around whether certain fatty acids are worse for promoting insulin resistance, inflammation, and obesity. The overall evidence in the literature suggests that medium-chain saturated fats (such as lauric acid, found in coconut oil) and monounsaturated fat (oleic acid, found in olive oil) are less likely to promote insulin resistance, inflammation, and fat storage compared to long-chain saturated fatty acids (such as stearic acid found in large quantities in butter, but particularly palmitic acid found in palm oil) especially when consumed on top of a diet moderate in refined carbohydrates. Compared to long-chain saturated fats, lauric acid and oleic acid have an increased fatty acid oxidation rate, are more likely to be burned for energy and less likely to be stored in adipose tissue, and thus promote increased energy expenditure. Omega-6 polyunsaturated fatty acids (PUFAs), such as linoleic acid, as found in vegetable oils may contribute to obesity, whereas omega-3 PUFA may be protective. Importantly, both olive oil as part of a Mediterranean diet, and omega-3 from fish and fish oil have been proven to reduce risk of cardiovascular (CV) events.

The Microvascular and Macrovascular Benefits of Fibrates in Diabetes and the Metabolic Syndrome: A review.

BACKGROUND: The purpose of this article is to discuss the evidence regarding potential macrovascular and microvascular benefits of fibrate therapy in general and fenofibrate specifically. METHODS: We performed a literature review summarizing the results of studies testing fibrates on relevant. RESULTS: Although statins are the first line therapy with an unparalleled amount of evidence for reducing the risk of cardiovascular disease (CVD) in patients with dyslipidemia and the metabolic syndrome (MetS), there are several landmark studies that have focused on the potential benefits of fibrate therapy for reducing CVD risk. Fibrates confer benefits mostly for patients with diabetes mellitus (DM), MetS, and atherogenic dyslipidemia. Recently, many studies have shown that fibrates confer benefits on the vascular system as well as the liver and kidneys. Fibrates also have demonstrable benefits in cohorts of patients with DM and renal disease. CONCLUSIONS: Fibrates appear to provide significant microvascular and macrovascular benefits particularly in patients with DM, MetS, or renal disease.