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.

The Importance of Maintaining a Low Omega-6/Omega-3 Ratio for Reducing the Risk of Autoimmune Diseases, Asthma, and Allergies.

Up until about 100 years ago, the omega-6/3 ratio has been around 4:1 or less. However, the typical Western diet now provides an omega-6/3 ratio of approximately 20:1 in favor of omega-6. This predisposes to supraphysiologic inflammatory responses and perpetuates chronic low-grade inflammation. The overconsumption of linoleic acid, mainly from industrial omega-6 seed oils, and the lack of long-chain omega-3s in the diet creates a pro-inflammatory, pro-allergic, pro-thrombotic state. Reducing the omega-6/3 ratio, particularly through reductions in the intake of refined omega-6 seed oil, and increasing the intake of marine omega-3s, either through dietary means or supplementation, may be an effective strategy for reducing inflammation, allergies, and autoimmune reactions.

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.