linoleic-acid and Coronary-Artery-Disease

Background We aimed at investigating the association of circulating fatty acids with coronary heart disease (CHD) and stroke risk. Methods and Results We conducted an individual-participant data meta-analysis of 5 UK-based cohorts and 1 matched case-control study. Fatty acids (ie, omega-3 docosahexaenoic acid, omega-6 linoleic acid, monounsaturated and saturated fatty acids) were measured at baseline using an automated high-throughput serum nuclear magnetic resonance metabolomics platform. Data from 3022 incident CHD cases (13 104 controls) and 1606 incident stroke cases (13 369 controls) were included. Logistic regression was used to model the relation between fatty acids and odds of CHD and stroke, adjusting for demographic and lifestyle variables only (ie, minimally adjusted model) or with further adjustment for other fatty acids (ie, fully adjusted model). Although circulating docosahexaenoic acid, but not linoleic acid, was related to lower CHD risk in the fully adjusted model (odds ratio, 0.85; 95% CI, 0.76-0.95 per standard unit of docosahexaenoic acid), there was evidence of high between-study heterogeneity and effect modification by study design. Stroke risk was consistently lower with increasing circulating linoleic acid (odds ratio for fully adjusted model, 0.82; 95% CI, 0.75-0.90). Circulating monounsaturated fatty acids were associated with higher CHD risk across all models and with stroke risk in the fully adjusted model (odds ratio, 1.22; 95% CI, 1.03-1.44). Saturated fatty acids were not related to increased CHD risk in the fully adjusted model (odds ratio, 0.94; 95% CI, 0.82-1.09), or stroke risk. Conclusions We found consistent evidence that linoleic acid was associated with decreased risk of stroke and that monounsaturated fatty acids were associated with increased risk of CHD. The different pattern between CHD and stroke in terms of fatty acids risk profile suggests future studies should be cautious about using composite events. Different study designs are needed to assess which, if any, of the associations observed is causal.

Topics: Adult; Aged; Biomarkers; Case-Control Studies; Coronary Artery Disease; Fatty Acids; Female; Heart Disease Risk Factors; Humans; Linoleic Acid; Male; Middle Aged; Prognosis; Protective Factors; Risk Assessment; Stroke; United Kingdom

Shortly after the discovery that linoleic acid was an essential fatty acid in 1930, α-linolenic acid also was reported to prevent the fatty acid deficiency syndrome in animals. However, several prominent laboratories could not confirm the findings with α-linolenic acid, and as a result there was a loss of interest in omega-3 fatty acids in lipid research. Even the findings that a prostaglandin can be synthesized from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is necessary for optimum retinal function generated only limited interest in omega-3 fatty acids. The breakthrough came in the 1970s when Dyerberg and Bang reported that the low incidence of atherosclerotic coronary disease in Greenland Eskimos was due to the high marine lipid content of their diet. They subsequently found that EPA, which was increased in Eskimo plasma, inhibited platelet aggregation, and they concluded that the low incidence of coronary artery disease was due to the anti-thrombotic effect of EPA. This stimulated widespread interest and research in EPA and DHA, leading to the present view that, like their omega-6 counterparts, omega-3 fatty acids have important physiological functions and are essential fatty acids.

Topics: Animals; Arachidonic Acid; Biomedical Research; Coronary Artery Disease; Coronary Thrombosis; Diet; Fatty Acids, Omega-3; Fibrinolytic Agents; Humans; Inuit; Linoleic Acid; Platelet Aggregation; Rats

To examine the traditional diet-heart hypothesis through recovery and analysis of previously unpublished data from the Minnesota Coronary Experiment (MCE) and to put findings in the context of existing diet-heart randomized controlled trials through a systematic review and meta-analysis.. The MCE (1968-73) is a double blind randomized controlled trial designed to test whether replacement of saturated fat with vegetable oil rich in linoleic acid reduces coronary heart disease and death by lowering serum cholesterol. Recovered MCE unpublished documents and raw data were analyzed according to hypotheses prespecified by original investigators. Further, a systematic review and meta-analyses of randomized controlled trials that lowered serum cholesterol by providing vegetable oil rich in linoleic acid in place of saturated fat without confounding by concomitant interventions was conducted.. One nursing home and six state mental hospitals in Minnesota, United States.. Unpublished documents with completed analyses for the randomized cohort of 9423 women and men aged 20-97; longitudinal data on serum cholesterol for the 2355 participants exposed to the study diets for a year or more; 149 completed autopsy files.. Serum cholesterol lowering diet that replaced saturated fat with linoleic acid (from corn oil and corn oil polyunsaturated margarine). Control diet was high in saturated fat from animal fats, common margarines, and shortenings.. Death from all causes; association between changes in serum cholesterol and death; and coronary atherosclerosis and myocardial infarcts detected at autopsy.. The intervention group had significant reduction in serum cholesterol compared with controls (mean change from baseline -13.8%v-1.0%; P<0.001). Kaplan Meier graphs showed no mortality benefit for the intervention group in the full randomized cohort or for any prespecified subgroup. There was a 22% higher risk of death for each 30 mg/dL (0.78 mmol/L) reduction in serum cholesterol in covariate adjusted Cox regression models (hazard ratio 1.22, 95% confidence interval 1.14 to 1.32; P<0.001). There was no evidence of benefit in the intervention group for coronary atherosclerosis or myocardial infarcts. Systematic review identified five randomized controlled trials for inclusion (n=10,808). In meta-analyses, these cholesterol lowering interventions showed no evidence of benefit on mortality from coronary heart disease (1.13, 0.83 to 1.54) or all cause mortality (1.07, 0.90 to 1.27).. Available evidence from randomized controlled trials shows that replacement of saturated fat in the diet with linoleic acid effectively lowers serum cholesterol but does not support the hypothesis that this translates to a lower risk of death from coronary heart disease or all causes. Findings from the Minnesota Coronary Experiment add to growing evidence that incomplete publication has contributed to overestimation of the benefits of replacing saturated fat with vegetable oils rich in linoleic acid.

Topics: Adult; Aged; Aged, 80 and over; Cause of Death; Cholesterol; Coronary Artery Disease; Coronary Disease; Diet, Fat-Restricted; Dietary Fats; Double-Blind Method; Female; History, 20th Century; Humans; Kaplan-Meier Estimate; Linoleic Acid; Male; Middle Aged; Minnesota; Myocardial Infarction; Plant Oils; Randomized Controlled Trials as Topic; Risk Factors; Young Adult

Although trans fatty acids (TFAs) may increase the risk of dyslipidemia and coronary artery disease (CAD), limited data are available on their association with heart failure (HF).. Our goal was to assess associations of plasma and dietary TFAs with HF and CAD.. We used a prospective, nested case-control design to select 788 incident HF cases and 788 matched controls from the Physicians' Health Study for biomarker analyses and a prospective cohort for the dietary analyses. Plasma fatty acids were assessed by using gas chromatography, and dietary intake was estimated by using a food-frequency questionnaire. Self-reported HF was ascertained by using annual follow-up questionnaires with validation in a subsample. We used conditional logistic (or Cox) regression to estimate multivariable-adjusted ORs (or HRs) for HF and CAD.. Multivariable-adjusted ORs (95% CIs) for HF across consecutive quintiles of plasma trans 18:2 (linoleic acid) fatty acids were 1.0 (reference), 1.10 (0.79, 1.54), 0.88 (0.62, 1.25), 0.71 (0.49, 1.02), and 0.67 (0.45, 0.98) (P-trend = 0.01). Each SD of plasma trans 18:2 was associated with a 22% lower risk of HF (95% CI: 6%, 36%). Plasma trans 16:1 and 18:1 were not associated with risk of HF (P > 0.05). Dietary trans fats were not associated with incident HF or CAD.. Our data are consistent with a lower risk of HF with higher concentrations of plasma trans 18:2 but not with trans 16:1 or trans 18:1 fatty acids in male physicians. Dietary TFAs were not related to incident HF or CAD.

Topics: Aged; Case-Control Studies; Coronary Artery Disease; Double-Blind Method; Heart Failure; Humans; Linoleic Acid; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Phospholipids; Proportional Hazards Models; Prospective Studies; Risk Factors; Self Report; Surveys and Questionnaires; Trans Fatty Acids

The delta-5 and delta-6 desaturases, encoded by FADS1 and FADS2 genes, are key enzymes in polyunsaturated fatty acid (PUFA) metabolism that catalyze the conversion of linoleic acid (LA) into arachidonic acid (AA) and that of alpha-linolenic acid (ALA) into eicosapentaenoic acid (EPA). Single-nucleotide polymorphisms (SNPs) in FADS1 and FADS2 have been associated with different concentrations of AA and LA, and those associations have possible functional consequences for desaturase activity.. We aimed to evaluate the possible association among FADS genotypes, desaturase activity, inflammation, and coronary artery disease (CAD).. Thirteen FADS SNPs and the ratio of AA to LA (AA/LA) on red blood cell (RBC) membranes, a marker of desaturase activity, were evaluated in 876 subjects with (n = 610) or without (n = 266) angiographically documented CAD.. Both AA/LA and the ratio of EPA to ALA (EPA/ALA) were higher in patients with CAD than in those without CAD, but, in a multiple logistic regression model, only a higher AA/LA resulted an independent risk factor for CAD (odds ratio: 2.55; 95% CI: 1.61, 4.05 for higher compared with lower ratio tertile; P for trend < 0.001). Furthermore, concentrations of high-sensitivity C-reactive protein increased progressively across tertiles of AA/LA. Graded increases in high-sensitivity C-reactive protein concentrations and CAD risk were related to the carriership of FADS haplotypes, including the alleles associated with a higher ratio.. In populations following a Western diet, subjects carrying FADS haplotypes that are associated with higher desaturase activity may be prone to a proinflammatory response favoring atherosclerotic vascular damage.

Topics: Arachidonic Acid; Coronary Artery Disease; Delta-5 Fatty Acid Desaturase; Erythrocyte Membrane; Fatty Acid Desaturases; Female; Gene Expression Regulation, Enzymologic; Haplotypes; Humans; Inflammation; Linoleic Acid; Linoleoyl-CoA Desaturase; Male; Middle Aged; Multigene Family; Polymorphism, Single Nucleotide; Risk Factors

Topics: Adult; Aged; Aged, 80 and over; alpha-Linolenic Acid; Animals; Arachidonic Acid; Coronary Artery Disease; Coronary Disease; Diet; Dietary Fats; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Greece; Humans; Japan; Linoleic Acid; Lipids; Male; Middle Aged; Neoplasms; Risk Factors; Stroke; United States

Topics: alpha-Linolenic Acid; Coronary Artery Disease; Dose-Response Relationship, Drug; Humans; Linoleic Acid

Epidemiologic studies suggest that a higher consumption of eicosapentaenoic acid and docosahexaenoic acid is associated with a reduced risk of cardiovascular disease. Studies in humans and animals also reported an inverse association between alpha-linolenic acid and cardiovascular disease morbidity and mortality.. We examined the relation between dietary linolenic acid and prevalent coronary artery disease (CAD).. We studied 4584 participants with a mean (+/-SD) age of 52.1 +/- 13.7 y in the National Heart, Lung, and Blood Institute Family Heart Study in a cross-sectional design. Participants' diets were assessed with a semiquantitative food-frequency questionnaire. For each sex, we created age- and energy-adjusted quintiles of linolenic acid, and we used logistic regression to estimate prevalent odds ratios for CAD.. From the lowest to the highest quintile of linolenic acid, the prevalence odds ratios of CAD were 1.0, 0.77, 0.61, 0.58, and 0.60 for the men (P for trend = 0.012) and 1.0, 0.57, 0.52, 0.30, and 0.42 for the women (P for trend = 0.014) after adjustment for age, linoleic acid, and anthropometric, lifestyle, and metabolic factors. Linoleic acid was also inversely related to the prevalence odds ratios of CAD in the multivariate model (0.60 and 0.61 in the second and third tertiles, respectively) after adjustment for linolenic acid. The combined effect of linoleic and linolenic acids was stronger than the individual effects of either fatty acid.. A higher intake of either linolenic or linoleic acid was inversely related to the prevalence odds ratio of CAD. The 2 fatty acids had synergistic effects on the prevalence odds ratio of CAD.

Topics: alpha-Linolenic Acid; Coronary Artery Disease; Cross-Sectional Studies; Drug Synergism; Female; Humans; Linoleic Acid; Male; Middle Aged; Odds Ratio; Prevalence; Regression Analysis; Risk Factors; Surveys and Questionnaires; United States