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

Circulation ◽  
2019 ◽  
Vol 140 (12) ◽  
Author(s):  
Ann C. Skulas-Ray ◽  
Peter W.F. Wilson ◽  
William S. Harris ◽  
Eliot A. Brinton ◽  
Penny M. Kris-Etherton ◽  
...  

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.

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Penson ◽  
S.S Martin ◽  
N.C Henney ◽  
M Banach

Abstract Background Low-density lipoprotein cholesterol (LDL-C) is an established risk factor for cardiovascular disease (CVD), and a target for lipid-lowering therapy. LDL-C is typically not measured directly but is estimated using the Friedewald formula, which assumes a fixed factor for the ratio of triglycerides (TG) to very low-density lipoprotein cholesterol (VLDL-C). However this assumption is sometimes not valid. The Martin/Hopkins (M/H) formula estimates LDL-C using an adjustable factor for the TG:VLDL-C ratio and is expected to improve upon Friedewald when predicting measured LDL-C, and apolipoprotein B (ApoB), one molecule of which is associated with each LDL particle. Purpose We compared values of LDL-C calculated by the Friedewald and M/H methods with respect to their correlation with non-high density lipoprotein cholesterol (non-HDL-C) and ApoB, and their classification of individuals based upon attainment of the threshold value of 70 mg/dl (1.8 mmol/l) of LDL-C. This cut-point is a treatment target for individuals at high risk of CVD in the 2019 ESC guidelines for lipid modification, and a threshold for initiating statin therapy in the 2019 ACC/AHA guidelines. Methods In this analysis we included participants in the National Health and Nutrition Examination Survey (NHANES) from 2005–2016, age ≥18, <80 years who had measurements for total cholesterol (TC), TG and HDL-C. LDL-C was calculated using Friedewald and M/H. We correlated LDL-C (calculated using the two methods) with non-HDL-C and ApoB. We identified individuals with LDL-C <70 mg/dl using both methods. When LDL-C (Friedewald) was <70, but LDL-C (M/H) was >70, we classified these participants as discordant. Statistical analyses were performed in IBM SPSS for Windows v26. Results 12,243 individuals were included. 51.8% were female, mean (±SD) age was 45.5±17.4, 15.3% were treated with statins, ApoB was available for 2179 participants. Mean lipid concentrations (mg/dl) were: TC: 191.5±41.0, TG: 120.0±67.0, HDL-C: 54.1±15.7, LDL-C (Friedewald): 113.3±35.4; LDL-C (M/H): 114.9±35.2. In the whole population, LDL-C (M/H) was more strongly correlated than LDL-C (Friedewald) with ApoB (r=0.935 v 0.894) and non-HDL-C (r=0.981 v 0.944). In statin-treated participants, LDL-C (M/H) was also more strongly correlated with ApoB (r=0.951 v 0.914) and non-HDL-C (r=0.979 v 0.928). 1139 participants had LDL-C (Friedewald) <70 mg/dl. Of these, 206 individuals (18.1%) were discordant, having LDL-C (M/H) >70 mg/dl. Amongst statin-treated patients, 22.9% were discordant. Only 5.5% of individuals with LDL-C (M/H) <70 mg/dl showed reverse discordance (LDL-C (Friedewald) >70 mg/dl). Conclusions The M/H method of calculating LDL-C correlates more strongly with non-HDL-C and ApoB than Friedewald. Importantly the discordant results confirm previous observations that Friedewald underestimates LDL-C at low concentrations. This may result in under-use of lipid-lowering therapies. Funding Acknowledgement Type of funding source: None


Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3422
Author(s):  
Kim Allan Williams ◽  
Ibtihaj Fughhi ◽  
Setri Fugar ◽  
Monica Mazur ◽  
Sharon Gates ◽  
...  

Introduction: The 2019 American College of Cardiology/American Heart Association (ACC/AHA) Prevention Guidelines emphasize reduction in dietary sodium, cholesterol, refined carbohydrates, saturated fat and sweetened beverages. We hypothesized that implementing this dietary pattern could reduce cardiovascular risk in a cohort of volunteers in an urban African American (AA) community church, during a 5-week ACC/AHA-styled nutrition intervention, assessed by measuring risk markers and adherence, called HEART-LENS (Helping Everyone Assess Risk Today Lenten Nutrition Study). Methods: The study population consisted of 53 volunteers who committed to eat only home-delivered non-dairy vegetarian meals (average daily calories 1155, sodium 1285 mg, cholesterol 0 mg; 58% carbohydrate, 17% protein, 25% fat). Body mass index (BMI) and fasting serum markers of cardiometabolic and risk factors were measured, with collection of any dietary deviation. Results: Of 53 volunteers, 44 (mean age 60.2 years, 37 women) completed the trial (88%); 1 was intolerant of the meals, 1 completed both blood draws but did not eat delivered food, and 7 did not return for the tests. Adherence to the diet was reported at 93% in the remaining 44. Cardiometabolic risk factors improved significantly, highlighted by a marked reduction in serum insulin (−43%, p = 0.000), hemoglobin A1c (6.2% to 6.0%, p = 0.000), weight and BMI (−10.2 lbs, 33 to 31 kg/m2, p = 0.000), but with small reductions of fasting glucose (−6%, p = 0.405) and triglyceride levels (−4%, p = 0.408). Additionally, improved were trimethylamine-N-oxide (5.1 to 2.9 µmol/L, −43%, p = 0.001), small dense low-density lipoprotein cholesterol (LDL) (24.2 to 19.1 mg/dL, −21%, p = 0.000), LDL (121 to 104 mg/dL, −14%, p = 0.000), total cholesterol (TC) (190 to 168 mg/dL, −12%, p = 0.000), and lipoprotein (a) (LP(a)) (56 to 51 mg/dL, −11%, p = 0.000); high sensitivity C-reactive protein (hs-CRP) was widely variable but reduced by 16% (2.5 to 2.1 ng/mL, p = NS) in 40 subjects without inflammatory conditions. Soluble urokinase plasminogen activator (suPAR) levels were not significantly changed. The ACC/AHA pooled cohort atherosclerotic cardiovascular disease (ASCVD) risk scores were calculated for 41 and 36 volunteers, respectively, as the ASCVD risk could not be calculated for 3 subjects with low lipid fractions at baseline and 8 subjects after intervention (p = 0.184). In the remaining subjects, the mean 10-year risk was reduced from 10.8 to 8.7%, a 19.4% decrease (p = 0.006), primarily due to a 14% decrease in low-density lipoprotein cholesterol and a 10 mm Hg (6%) reduction in systolic blood pressure. Conclusions: In this prospective 5-week non-dairy vegetarian nutrition intervention with good adherence consistent with the 2019 ACC/AHA Guidelines in an at-risk AA population, markers of cardiovascular risk, cardiometabolism, and body weight were significantly reduced, including obesity, low-density lipoprotein cholesterol (LDLc) density, LP(a), inflammation, and ingestion of substrates mediating production of trimethylamine-N-oxide (TMAO). Albeit reduced, hs-CRP and suPAR, were not lowered consistently. This induced a significant decrease in the 10-year ASCVD risk in this AA cohort. If widely adopted, this could dramatically reduce and possibly eradicate, the racial disparity in ASCVD events and mortality, if 19% of the 21% increase is eliminated by this lifestyle change.


Author(s):  
Fotios Barkas ◽  
Tzortzis Nomikos ◽  
Evangelos Liberopoulos ◽  
Demosthenes Panagiotakos

Background: Although a cholesterol-lowering diet and the addition of plant sterols and stanols are suggested for the lipid management of children and adults with familial hypercholesterolemia, there is limited evidence evaluating such interventions in this population. Objectives: To investigate the impact of cholesterol-lowering diet and other dietary interventions on the incidence or mortality of cardiovascular disease and lipid profile of patients with familial hypercholesterolemia. Search methods: Relevant trials were identified by searching US National Library of Medicine National Institutes of Health Metabolism Trials Register and clinicaltrials.gov.gr using the following terms: diet, dietary, plant sterols, stanols, omega-3 fatty acids, fiber and familial hypercholesterolemia. Selection criteria: Randomized controlled trials evaluating the effect of cholesterol-lowering diet or other dietary interventions in children and adults with familial hypercholesterolemia were included. Data collection and analysis: Two authors independently assessed the trial eligibility and bias risk and one extracted the data, with independent verification of data extraction by a colleague. Results: A total of 17 trials were finally included, with a total of 376 participants across 8 comparison groups. The included trials had either a low or unclear bias risk for most of the parameters used for risk assessment. Cardiovascular incidence or mortality were not evaluated in any of the included trials. Among the planned comparisons regarding patients’ lipidemic profile, a significant difference was noticed for the following comparisons and outcomes: omega-3 fatty acids reduced triglycerides (mean difference [MD]: -0.27 mmol/L, 95% confidence interval [CI]: -0.47 to -0.07, p<0.01) when compared with placebo. A non-significant trend towards a reduction in subjects’ total cholesterol (MD: -0.34, 95% CI: -0.68 to 0, mmol/L, p=0.05) and low-density lipoprotein cholesterol (MD: -0.31, 95% CI: -0.61 to 0, mmol/L, p=0.05) was noticed. In comparison with cholesterol-lowering diet, the additional consumption of plant stanols decreased total cholesterol (MD: -0.62 mmol/l, 95% CI: -1.13 to -0.11, p=0.02) and low-density lipoprotein cholesterol (MD: -0.58 mmol/l, 95% CI: -1.08 to -0.09, p=0.02). The same was by plant sterols (MD: -0.46 mmol/l, 95% CI: -0.76 to -0.17, p<0.01 for cholesterol, and MD: -0.45 mmol/l, 95% CI: -0.74 to -0.16, p<0.01 for low-density lipoprotein cholesterol). No heterogeneity was noticed among the studies included in these analyses. Conclusions: Available trials confirm that the addition of plant sterols or stanols has a cholesterol-lowering effect on such individuals. On the other hand, supplementation with omega-3 fatty acids effectively reduces triglycerides and might have a role in lowering the cholesterol of patients with familial hypercholesterolemia. Additional studies are needed to investigate the effectiveness of a cholesterol-lowering diet or the addition of soya protein and dietary fibers to a cholesterol-lowering diet in familial hypercholesterolemia.


2018 ◽  
Author(s):  
Mohamad Saleh ◽  
Francine K Welty

Cardiovascular disease (CVD), the leading cause of death in industrialized countries, is a dietary disease. In this review, we summarize the evidence from prospective, observational studies and randomized primary and secondary prevention trials of various diets supporting a role of dietary components in the development of CVD and in lowering low-density lipoprotein cholesterol (LDL-C) and cardiovascular events. The role of saturated fat in raising cholesterol and triglyceride is discussed, as well as studies showing that elevated levels of both LDL-C and triglyceride increase the risk of atherosclerosis and that lowering of LDL-C lowers the risk of CVD and its clinical sequelae, including unstable angina, myocardial infarction, and death. Randomized trials of omega-3 fatty acids and the Mediterranean diet and CVD outcomes are reviewed. Classification and causes of various types of hypercholesterolemia and hypertriglyceridemia are summarized. Finally, guidelines for nutritional management and treatment of these lipid disorders to lower levels of LDL-C and triglyceride and prevent CVD are provided.  This review contains 4 figures, 5 tables and 64 references Key words: cardiovascular disease, coronary heart disease, lipids, low-density lipoprotein cholesterol, Mediterranean diet, nutrition, saturated fat, triglyceride 


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