Autoantibody against oxidised LDL and progression of carotid atherosclerosis Effects of a high-dose concentrate of n-3 fatty acids or corn oil introduced early after an acute myocardial infarction on serum triacylglycerol and HDL cholesterol. Effects of altering the ratio of dietary n-6 to n-3 fatty acids on insulin sensitivity, lipoprotein size, and postprandial lipemia in men and postmenopausal women aged 45-70 y: the OPTILIP Study. Fish intake is associated with a reduced progression of coronary artery atherosclerosis in postmenopausal women with coronary artery disease. Effect of an increased intake of alpha-linolenic acid and group nutritional education on cardiovascular risk factors: the Mediterranean Alpha-linolenic Enriched Groningen Dietary Intervention (MARGARIN) study. Effects of a Monounsaturated Fatty Acid–Enriched Hypocaloric Diet on Cardiovascular Risk Factors in Obese Patients With Type 2 Diabetes Increased α-linolenic acid intake lowers C-reactive protein, but has no effect on markers of atherosclerosis The effect of the plasma n-3/n-6 polyunsaturated fatty acid ratio on the dietary LDL phenotype transformation - insights from the LIPGENE study. Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial
Oxidative modification of LDL renders it immunogenic and autoantibodies to epitopes of oxidised LDL , such as malondialdehyde (MDA)-lysine , are found in serum and recognise material in atheromatous tissue . However , there has been no prospect i ve study to assess the importance of oxidised LDL among patients with vascular disease . We compared the titre of  autoantibodies to MDA-modified LDL and native LDL in baseline serum sample s of 30 eastern Finnish men with accelerated two-year progression of carotid atherosclerosis and 30 age-matched controls without progression . Neither group had specific antibody binding to native LDL . A titre was defined as a ratio of antibody binding to MDA-LDL/binding to native LDL . Cases had a significantly higher titre to MDA-LDL ( 2.67 vs 2.06 , p = 0.003 ) . Cases also had a greater proportion of smokers ( 37 % vs 3 % ) , higher LDL cholesterol ( 4.2 mmol/l vs 3.6 mmol/l ) , and higher serum copper concentration ( 1.14 mg/l vs 1.04 mg/l ) . Even after adjusting for these variables and the severity of baseline atherosclerosis , the difference in antibody titre remained significant in a multifactorial logistic model ( p = 0.031 ) . Thus , the titre of autoantibodies to MDA-LDL was an independent predictor of the progression of carotid atherosclerosis in these Finnish men . Our data provide further support for a role of oxidatively modified LDL in atherogenesis BACKGROUND Results of epidemiologic studies and clinical trials indicate that moderate doses of n-3 fatty acids reduce the risk of cardiovascular disease and may improve prognosis . OBJECTIVE The objective was to evaluate the effect of a high-dose ethylester concentrate of n-3 fatty acids administered early after an acute myocardial infa rct ion ( MI ) on subsequent cardiac events and serum lipids . DESIGN Three hundred patients with acute MI were r and omly assigned to a daily dose of either 4 g highly concentrated n-3 fatty acids or corn oil , administered in a double-blind manner over 12 - 24 mo . Median follow-up time was 1.5 y. Clinical follow-up , including the drawing of blood sample s , was performed after 6 wk of treatment and later at 0.5-year intervals . RESULTS Forty-two ( 28 % ) patients in the n-3 group and 36 ( 24 % ) in the corn oil group experienced at least one cardiac event ( cardiac death , resuscitation , recurrent MI , or unstable angina ) . No significant difference in prognosis was observed between groups for single or combined cardiac events . Total cholesterol concentrations decreased in both groups , with no significant intergroup differences . On average , the monthly increase in HDL cholesterol was 1.11 % in the n-3 group and 0.55 % in the corn oil group ( P = 0.0016 ) . Triacylglycerol concentrations decreased by 1.30%/mo in the n-3 group , whereas they increased by 0.35%/mo in the corn oil group ( P < 0.0001 ) . CONCLUSION No clinical benefit of a high-dose concentrate of n-3 fatty acids compared with corn oil was found despite a favorable effect on serum lipids BACKGROUND Insulin resistance is associated with elevated plasma triacylglycerol , low HDL concentrations , elevated postpr and ial lipemia , and a predominance of small , dense LDLs ( sdLDLs ) . It has been hypothesized that the dietary ratio of n-6 to n-3 ( n-6:n-3 ) polyunsaturated fatty acids ( PUFAs ) may have favorable effects on these risk factors by increasing insulin sensitivity . OBJECTIVE The objective was to measure changes in insulin sensitivity , lipoprotein size , and postpr and ial lipemia after a 6-mo alteration in n-6:n-3 . DESIGN In a r and omized , parallel design in 258 subjects aged 45 - 70 y , we compared 4 diets providing 6 % of energy as PUFAs with an n-6:n-3 between 5:1 and 3:1 with a control diet that had an n-6:n-3 of 10:1 . The diets were enriched in alpha-linolenic acid , eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , or both . Insulin sensitivity was assessed with the homeostatic model assessment of insulin resistance and the revised quantitative insulin sensitivity test . RESULTS Dietary intervention did not influence insulin sensitivity or postpr and ial lipase activities . Fasting and postpr and ial triacylglycerol concentrations were lower , and the proportion of sdLDLs decreased ( by 12.7 % ; 95 % CI : -22.9 % , 2.4 % ) , with an n-6:n-3 of approximately 3:1 , which was achieved by the addition of long-chain n-3 PUFAs ( EPA and DHA ) . CONCLUSIONS Decreasing the n-6:n-3 does not influence insulin sensitivity or lipase activities in older subjects . The reduction in plasma triacylglycerol after an increased intake of n-3 long-chain PUFAs results in favorable changes in LDL size BACKGROUND Higher intakes of fish and n-3 fatty acids are associated with a reduced risk of cardiovascular events and mortality . However , limited data exist on the effect of fish intake on actual measures of progression of coronary artery atherosclerosis . OBJECTIVE The aim was to examine the association between fish intake and the progression of coronary artery atherosclerosis in women with coronary artery disease . DESIGN This was a prospect i ve cohort study of postmenopausal women ( n = 229 ) participating in the Estrogen Replacement and Atherosclerosis trial . Usual fish intake was estimated at baseline with a food-frequency question naire . Quantitative coronary angiography was performed at baseline and after 3.2 + /- 0.6 ( x + /- SD ) y to evaluate changes in the mean minimum coronary artery diameter , the mean percentage of stenosis , and the development of new coronary lesions . RESULTS Compared with lower fish intakes , consumption of > or = 2 servings of fish or > or = 1 serving of tuna or dark fish per week was associated with smaller increases in the percentage of stenosis ( 4.54 + /- 1.37 % compared with -0.06 + /- 1.59 % and 5.12 + /- 1.48 % compared with 0.35 + /- 1.47 % , respectively ; P < 0.05 for both ) in diabetic women after adjustments for age , cardiovascular disease risk factors , and dietary intakes of fatty acids , cholesterol , fiber , and alcohol . These associations were not significant in nondiabetic women . Higher fish consumption was also associated with smaller decreases in minimum coronary artery diameter and fewer new lesions . CONCLUSIONS Consumption of fish is associated with a significantly reduced progression of coronary artery atherosclerosis in women with coronary artery disease BACKGROUND The effect of long-term increased intakes of alpha-linolenic acid ( ALA ; 18:3n-3 ) on cardiovascular risk factors is unknown . OBJECTIVES Our objectives were to assess the effect of increased ALA intakes on cardiovascular risk factors and the estimated risk of ischemic heart disease ( IHD ) at 2 y and the effect of nutritional education on dietary habits . DESIGN Subjects with multiple cardiovascular risk factors ( 124 men and 158 women ) were r and omly assigned in a double-blind fashion to consume a margarine rich in either ALA [ 46 % linoleic acid ( LA ; 18:2n-6 ) and 15 % ALA ; n = 114 ] or LA ( 58 % LA and 0.3 % ALA ; n = 168 ) . An intervention group ( n = 110 ; 50 % ALA ) obtained group nutritional education , and a control group ( n = 172 ; 34 % ALA ) received a posted leaflet containing the st and ard Dutch dietary guidelines . RESULTS Average ALA intakes were 6.3 and 1.0 g/d in the ALA and LA groups , respectively . After 2 y , the ALA group had a higher ratio of total to HDL cholesterol ( + 0.34 ; 95 % CI : 0.12 , 0.56 ) , lower HDL cholesterol ( -0.05 mmol/L ; -0.10 , 0 ) , higher serum triacylglycerol ( + 0.24 mmol/L ; 0.02 , 0.46 ) , and lower plasma fibrinogen ( -0.18 g/L ; -0.31 , -0.04 ; after 1 y ) than did the LA group ( adjusted for baseline values , sex , and lipid-lowering drugs ) . No significant difference existed in 10-y estimated IHD risk . After 2 y , the intervention group had lower saturated fat intakes and higher fish intakes than did the control group . CONCLUSIONS Increased ALA  intakes decrease the estimated IHD risk to an extent similar to that found with increased LA intakes . Group nutritional education can effectively increase fish intake OBJECTIVE To determine whether the lipoprotein response to weight loss in obese patients with type 2 diabetes can be improved by modifying the macronutrient composition of the commonly prescribed low-fat , high-carbohydrate ( CHO ) hypocaloric diet . RESEARCH DESIGN AND METHODS Nine obese patients with type 2 diabetes were treated with a monounsaturated fatty acid (MUFA)-enriched weight-reducing formula diet and compared with eight obese patients with type 2 diabetes treated with a low-fat , high-CHO weight-reducing formula diet .  Weight loss ensued for 6 weeks , followed by 4 weeks of refeeding using isocaloric formulas enriched with MUFA or CHO , respectively . Fasting blood sample s were obtained to measure plasma lipoproteins and LDL susceptibility to oxidation ( measured as lag time : time required to induce in vitro formation of conjugated dienes ) . RESULTS At baseline , there were no differences between the groups in plasma lipids , lipoproteins , or LDL susceptibility to oxidation . Weight loss was similar between the groups . Dieting result ed in decreases in total plasma cholesterol , LDL , HDL , triglycerides , and apolipoproteins A and B ( P < 0.05 ) , but the MUFA group manifested a greater decrease in total cholesterol , triglycerides , and apolipoprotein B and a smaller decrease in HDL and apolipoprotein A than the CHO group ( P < 0.05 ) . Improvements in these parameters were sustained during refeeding . After dieting , lag time was prolonged in the MUFA group ( 208 ± 10 min ) compared with the CHO group ( 146 ± 11 min ; P < 0.05 ) . Lag time was prolonged further during refeeding in the MUFA group ( 221 ± 13 min , P = 0.10 ) , while the CHO group remained unchanged ( 152 ± 9 min , P < 0.05 ) . Lag time correlated strongly with the oleic acid content of LDL after dieting and refeeding ( r = 0.74 and r = 0.93 , respectively ; both P < 0.001 ) . CONCLUSIONS Macronutrient content is an important determinant of the lipoprotein response to weight loss in obese patients with type 2 diabetes . MUFA-enriched hypocaloric diets potentiate the beneficial effects of weight loss to ameliorate cardiovascular risk factors in obese patients with type 2 diabetes Objective : To investigate the effects of increased alpha-linolenic acid (ALA)-intake on intima – media thickness ( IMT ) , oxidized low-density lipoprotein ( LDL ) antibodies , soluble intercellular adhesion molecule-1 ( sICAM-1 ) , C-reactive protein ( CRP ) , and interleukins 6 and 10 . Design : R and omized double-blind placebo-controlled trial . Subjects : Moderately hypercholesterolaemic men and women ( 55±10 y ) with two other cardiovascular risk factors (n=103).Intervention : Participants were assigned to a margarine enriched with ALA ( fatty acid composition 46 % LA , 15 % ALA ) or linoleic acid ( LA ) ( 58 % LA , 0.3 % ALA ) for 2 y. Results : Dietary ALA intake was 2.3 en% among ALA users , and 0.4 en% among LA users . The 2-y progression rate of the mean carotid IMT  ( ALA and LA : + 0.05 mm ) and femoral IMT ( ALA:+0.05 mm ; LA:+0.04 mm ) was similar , when adjusted for confounding variables . After 1 and 2 y , ALA users had a lower CRP level than LA users ( net differences −0.53 and −0.56 mg/l , respectively , P<0.05 ) . No significant effects were observed in oxidized LDL antibodies , and levels of sICAM-1 , interleukins 6 and 10 . Conclusions : A six-fold increased ALA intake lowers CRP , when compared to a control diet high in LA . The present study found no effects on markers for atherosclerosis . Sponsorship : The Dutch ‘ Praeventiefonds ’ BACKGROUND & AIMS LDL phenotype B is associated with obesity , insulin resistance , hypertriglyceridemia and oxidative stress . The effect of plasma n-3/n-6 PUFA ratio on LDL phenotype transformation was investigated . METHODS Patients with metabolic syndrome ( n=99 ) received one of four isocaloric diets : ( A ) High-fat ( 38 % energy ) SFA-rich diet ( HSFA ) ; ( B ) High-fat ( 38 % energy ) , MUFA-rich diet ( HMUFA ) ; ( C ) , low-fat ( LF ) ( 28 % energy ) , high-complex carbohydrate diet with 1.24g/d oleic sunflower oil ( LFHCC ) and ( D ) : low-fat ( 28 % energy ) , high-complex carbohydrate diet , with 1.24g/d LC n-3 PUFA ( LFHCC n-3 ) for 12 weeks . Analysis of plasma lipid profile and LDL phenotype was done pre- and post- interventions . RESULTS Post-dietary change of LDL density was a main effect observed in all groups . LFHCC n-3 and HFMUFA diets result ed in favorable alteration of LDL phenotype from B to A and decreased LDL density . In contrast , increased LDL density was observed in HSFA and LFHCC groups . The plasma pre-n3/n6 PUFA , Apo E change and pre-Apo CIII/CII ratios explained in 65 % the post-dietary change of LDL density in diet LFHCC n-3 consumers . CONCLUSIONS Study demonstrates efficacy of dietary n-3 PUFA to modify pro-atherogenic to less atherogenic LDL phenotype in patients with metabolic syndrome . Study identifier at Clinical Trials.gov was NCT00429195 BACKGROUND N-3 polyunsaturated fatty acids ( PUFAs ) from oily fish protect against death from cardiovascular disease . We aim ed to assess the hypothesis that incorporation of n-3 and n-6 PUFAs into advanced atherosclerotic plaques increases and decreases plaque stability , respectively . METHODS We did a r and omised controlled trial of patients awaiting carotid endarterectomy . We r and omly allocated patients control , sunflower oil ( n-6 ) , or fish-oil ( n-3 ) capsules until surgery . Primary outcome was plaque morphology indicative of stability or instability , and outcome measures were concentrations of EPA , DHA , and linoleic acid in carotid plaques ; plaque morphology ; and presence of macrophages in plaques . Analysis was per protocol . FINDINGS 188 patients were enrolled and r and omised ; 18 withdrew and eight were excluded . Duration of oil treatment was 7 - 189 days ( median 42 ) and did not differ between groups . The proportions of EPA and DHA were higher in carotid plaque fractions in patients receiving fish oil compared with those receiving control ( absolute difference 0.5 [ 95 % CI 0.3 - 0.7 ] , 0.4 [ 0.1 - 0.6 ] , and 0.2 [ 0.1 - 0.4 ] g/100 g total fatty acids for EPA ; and 0.3 [ 0.0 - 0.8 ] , 0.4 [ 0.1 - 0.7 ] , and 0.3 [ 0.1 - 0.6 ] g/100 g total fatty acids for DHA ; in plaque phospholipids , cholesteryl esters , and triacylglycerols , respectively ) . Sunflower oil had little effect on the fatty acid composition of lipid fractions . Fewer plaques from patients being treated with fish oil had thin fibrous caps and signs of inflammation and more plaques had thick fibrous caps and no signs of inflammation , compared with plaques in patients in the control and sunflower oil groups ( odds ratio 0.52 [ 95 % CI 0.24 - 0.89 ] and 1.19 [ 1.02 - 1.57 ] vs control ; 0.49 [ 0.23 - 0.90 ] and 1.16 [ 1.01 - 1.53 ] vs sunflower oil ) . The number of macrophages in plaques from patients receiving fish oil was lower than in the other two groups . Carotid plaque morphology and infiltration by macrophages did not differ between control and sunflower oil groups . INTERPRETATION Atherosclerotic plaques readily incorporate n-3 PUFAs from fish-oil supplementation , inducing changes that can enhance stability of atherosclerotic plaques . By contrast , increased consumption of n-6 PUFAs does not affect carotid plaque fatty-acid composition or stability over the time course studied here . Stability of plaques could explain reductions in non-fatal and fatal cardiovascular events associated with increased n-3 PUFA intake
The intake of omega-6 vegetable oils , particularly soybean oil , began to increase in the USA starting in the early 1900s at a time when the consumption of butter and lard was on the decline.1 This caused a more than two-fold increase in the intake of linoleic acid , the main omega-6 polyunsaturated fat found in vegetable oils , which now makes up around 8 % to 10 % of total energy intake in the Western world .
The omega-6 fat linoleic acid should not be confused with conjugated linoleic acid found in pastured animal foods .
It has been known for decades that linoleic acid , as a percentage of total fatty acids in lipids , is reduced in patients with CAD , and this has been used as an argument to