Arja T. Erkkilä

Comparison of the effects of plant sterol ester and plant stanol ester-enriched margarines in lowering serum cholesterol concentrations in hypercholesterolaemic subjects on a low-fat diet.

Objective: To investigate cholesterol-lowering effects of stanol ester (STAEST) and sterol ester (STEEST)-enriched margarines as part of a low-fat diet.Design: According to a Latin square model randomized double-blind repeated measures design with three test margarines and three periods.Setting: Outpatient clinical trial with free-living subjects.Subjects: Thirty-four hypercholesterolaemic subjects completed the study.Interventions: Subjects consumed three rapeseed oil-based test margarines (STAEST, STEEST and control (no added stanols or sterols)) as part of a low-fat diet each for 4 weeks.Results: Mean daily intake of total plant sterols plus stanols was 2.01–2.04 g during the two test margarine periods. In reference to control, serum total cholesterol was reduced by 9.2 and 7.3% with the STAEST and STEEST margarine, respectively (P<0.001 for both). The respective reductions for low-density lipoprotein (LDL) cholesterol were 12.7 and 10.4% (P<0.001). The cholesterol-lowering effects of the test margarines did not differ significantly. The presence of apolipoprotein E4 allele had a significant effect on LDL cholesterol response during the STAEST margarine only. Serum sitosterol and campesterol increased by 0.83 and 2.77 mg/l with the STEEST (P<0.001), respectively and decreased by 1.18 and 2.60 mg/l with the STAEST margarine (P<0.001). Increases of serum sitostanol and campestanol were 0.11 and 0.19 mg/l with the STAEST margarine (P<0.001), repsectively. No significant changes were found in serum fat-soluble vitamin and carotenoid concentrations when related to serum total cholesterol.Conclusions: STAEST and STEEST margarines reduced significantly and equally serum total and LDL cholesterol concentrations as part of a low-fat diet.Sponsorship: Grant to the University of Kuopio by Raisio Benecol Ltd, Raisio, Finland.European Journal of Clinical Nutrition (2000) 54, 715–725

Dietary fatty acids and cardiovascular disease: an epidemiological approach.

The quality of dietary fat in relation to cardiovascular disease forms the basis of the diet-heart hypothesis. Current recommendations on dietary fat now emphasise quality rather than quantity. The focus of this review is to summarise the results from prospective cohort studies on dietary fat and cardiovascular disease outcomes. Relatively few prospective cohort studies have found an association between dietary fat quality and cardiovascular disease, partly because of limitations in estimating dietary intake. Saturated and trans fatty acids have increased cardiovascular risk in several studies. Both n-6 and n-3 polyunsaturated fatty acids have been associated with lower cardiovascular risk. Within the n-6 series, linoleic acid seems to decrease cardiovascular risk. Within the n-3 series the long-chain fatty acids (eicosapentaenoic and docosahexaenoic acids) are associated with decreased risk for especially fatal coronary outcomes, whereas the role of alpha-linolenic acid is less clear. Dietary fat quality also influences the activity of enzymes involved in the desaturation of fatty acids in the body. Serum desaturase indices have been consistently associated with adverse cardiovascular outcomes. Data from metabolic and clinical studies reinforce findings from observational studies supporting recommendations to replace saturated and trans fat with unsaturated fat in the prevention of cardiovascular disease.

Fiber and cardiovascular disease risk: how strong is the evidence?

Dietary fiber consists of edible parts of plants or analogous carbohydrates that are resistant to digestion and absorption in the human small intestine. Fiber can be classified as a dietary source (eg, cereal, fruit, vegetable, or legume) or as a supplement. Based on chemical properties, fiber can be divided to water-soluble (eg, &bgr;-glucans, pectin, and guar) and insoluble (eg, cellulose and lignin) forms. An increasing number of observational findings have reported a lower incidence of coronary heart disease in subjects who report consuming diets high in fiber. Dietary fiber is thought to affect several cardiovascular disease (CVD) risk factors. Soluble fiber decreases serum total and low-density lipoprotein cholesterol concentrations and improves insulin resistance. The effect of fiber on inflammatory markers and coagulation is not yet well established. While soluble, gel-forming fiber has beneficially affected CVD risk factors, food sources of mainly insoluble fibers, primarily contributed by cereal products, have been the most consistently associated with lower incidence rates of CVD. Despite this contradiction, the evidence promotes a food-based approach favoring increased intake of whole-grain cereals, fruit, and vegetables providing a mixture of different types of fibers for CVD prevention.

Autoantibodies Against Oxidized Low-Density Lipoprotein and Cardiolipin in Patients With Coronary Heart Disease

Autoantibodies against oxidized low density lipoprotein (oxLDL) have been proposed to be independent predictors of atherosclerotic vascular disease. Because the levels of autoantibodies against oxLDL and cardiolipin might be modified by the presentation and severity of coronary heart disease (CHD), we measured their levels in patients with different manifestations of CHD (n=415, mean age 61 years, range 33 to 74 years) in a subset of the European Action on Secondary Prevention through Intervention to Reduce Events (EUROASPIRE) study. There were 109 patients with coronary artery bypass surgery, 106 patients with balloon angioplasty, 101 patients with acute myocardial infarction, and 99 patients with acute myocardial ischemia. Autoantibodies were measured by ELISA. Food records and fatty acid profiles of serum cholesteryl esters were used to evaluate dietary intake. Anti-oxLDL antibodies were significantly higher in the group with acute myocardial infarction than in other groups in men (coronary artery bypass surgery 1.91+/-1. 41, balloon angioplasty 2.11+/-2.19, acute myocardial infarction 2. 52+/-2.05, and acute myocardial ischemia 1.96+/-1.78; P=0.022, mean+/-SD) but not in women. The titers of anti-cardiolipin antibodies did not differ among the patient groups. Neither of the autoantibodies was associated with recurrent coronary events. Anti-oxLDL and anti-cardiolipin autoantibodies were not correlated with serum total cholesterol, high density lipoprotein cholesterol, or triglycerides, except that in women anti-oxLDL antibodies and triglycerides were positively correlated (r=0.225, P=0.011). In men, anti-cardiolipin antibodies were higher in the lowest quartiles of dietary intakes of vitamin E and polyunsaturated fat. Dietary intakes of vitamin E and polyunsaturated fat were correlated (r=0. 588, P<0.001). In conclusion, autoantibodies against oxLDL were associated with myocardial infarction in men. Anti-cardiolipin autoantibodies were inversely correlated with dietary intakes of vitamin E and polyunsaturated fat in men with CHD.

Fatty fish intake decreases lipids related to inflammation and insulin signaling--a lipidomics approach.

Background The evidence of the multiple beneficial health effects of fish consumption is strong, but physiological mechanisms behind these effects are not completely known. Little information is available on the effects of consumption of different type of fish. The aim of this study was to investigate how fatty fish or lean fish in a diet affect serum lipidomic profiles in subjects with coronary heart disease. Methodology and Principal Findings A pilot study was designed which included altogether 33 subjects with myocardial infarction or unstable ischemic attack in an 8-week parallel controlled intervention. The subjects were randomized to either fatty fish (n = 11), lean fish (n = 12) or control (n = 10) groups. Subjects in the fish groups had 4 fish meals per week and subjects in the control group consumed lean beef, pork and chicken. A fish meal was allowed once a week maximum. Lipidomics analyses were performed using ultra performance liquid chromatography coupled to electrospray ionization mass spectrometry and gas chromatography. Multiple bioactive lipid species, including ceramides, lysophosphatidylcholines and diacylglycerols, decreased significantly in the fatty fish group, whereas in the lean fish group cholesterol esters and specific long-chain triacylglycerols increased significantly (False Discovery Rate q-value <0.05). Conclusions/Significance The 8-week consumption of fatty fish decreased lipids which are potential mediators of lipid-induced insulin resistance and inflammation, and may be related to the protective effects of fatty fish on the progression of atherosclerotic vascular diseases or insulin resistance. Trial Registration ClinicalTrials.gov NCT00720655

Higher plasma docosahexaenoic acid is associated with reduced progression of coronary atherosclerosis in women with CAD

Fish intake, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and in some cases α-linolenic acid (ALA) have been associated with reduced risk of cardiovascular events and death. The association between n-3 fatty acids in plasma lipids and the progression of coronary artery atherosclerosis was assessed among women with established coronary artery disease (CAD). A prospective cohort study involved postmenopausal women (n = 228) participating in the Estrogen Replacement and Atherosclerosis Trial. Quantitative coronary angiography was performed at baseline and after 3.2 ± 0.6 (mean ± SD) years. Women with plasma phospholipid (PL) DHA levels above the median, compared with below, exhibited less atherosclerosis progression, as expressed by decline in minimum coronary artery diameter (−0.04 ± 0.02 and −0.10 ± 0.02 mm, respectively; P = 0.007) or increase in percentage stenosis (1.34 ± 0.76% and 3.75 ± 0.74%, respectively; P = 0.006), and had fewer new lesions [2.0% (0.5–3.5%) of measured segments (95% confidence interval) and 4.2% (2.8–5.6%), respectively; P = 0.009] after adjustments for cardiovascular risk factors. Similar results were observed for DHA in the triglycerides (TGs). EPA and ALA in plasma lipids were not significantly associated with atherosclerosis progression. Consistent with higher reported fish intake, higher levels of plasma TG and PL DHA are associated with less progression of coronary atherosclerosis in postmenopausal women with CAD.

Diet in relation to socioeconomic status in patients with coronary heart disease

Objectives: Nutrient intake, food consumption and fatty acid profile of serum cholesteryl esters (CE) were investigated in relation to education in patients with coronary heart disease (CHD).Design: A cross-sectional survey in CHD patients selected from hospital records at least six months after hospitalisation. Food record, a questionnaire on dietary fat and fatty acid profile of CE were used to examine diet composition. Years of education, divided into three categories, were used to indicate socioeconomic status.Setting: The district of Kuopio University Hospital in Finland.Subjects: One hundred and nine patients with coronary artery bypass surgery, 106 patients with coronary angioplasty, 101 patients with acute myocardial infarction and 99 patients with acute myocardial ischaemia aged 61 y (33–74 y) (mean (range)).Results: Men with a low level of schooling had a higher intake of total and saturated fat, a lower consumption of vegetables and fruits, more frequently used butter or butter based spread and less frequently used oil compared to the diets of men with middle or high education. Men with low or middle education had a lower intake of alcohol than men with a high level of education. Highly-educated women had a lower proportion of myristic acid in CE than low-educated women and a similar trend between myristic acid and educational level was found in men.Conclusions: The educational level of men with CHD influenced their nutrient intake and food consumption, but in women with CHD its impact seemed to be weaker.Sponsorship: The Finnish Cultural Foundation, The Finnish Cultural Foundation of Northern Savo, The Aarne and Aili Turunen Foundation, The Finnish Foundation for Cardiovascular Research.

Vitamin K intake and atherosclerosis

Purpose of review It has been hypothesized that insufficient intake of vitamin K may increase soft-tissue calcification owing to impaired γ-carboxylation of the vitamin K-dependent protein matrix γ-carboxyglutamic acid. The evidence to support this putative role of vitamin K intake in atherosclerosis is reviewed. Recent findings In animal models, multiple forms of vitamin K have been shown to reverse the arterial calcification created by vitamin K antagonists. The human data, however, are less consistent. Phylloquinone, the primary dietary form, has not been associated consistently with the risk of cardiovascular diseases. High menaquinone intake may be associated with lower risk of coronary heart disease mortality, but this needs to be confirmed. Summary The role of vitamin K in calcification remains controversial. Although biologically plausible, results from the human studies have not consistently supported this hypothesis.

Evaluation and characterization of EIA measuring autoantibodies against oxidized LDL

Autoantibodies against oxidized LDL (oxLDL) have been measured in many laboratories. Comparison of data between laboratories is difficult because of methodological variations and differences in the expression of results. We have optimized an enzyme immunoassay (EIA), which measures autoantibodies against oxLDL and evaluated the effect on results of different ways of expressing the data. Optimized conditions were as follows: coating concentration 2 microg/ml of LDL on polysorp plates, 1% human serum albumin (HSA) as a blocking agent, sample dilution 1:50, conjugate dilution 1:8000, and 0.2% HSA in sample and conjugate diluents. The amount of autoantibodies expressed as ratios between oxLDL and native LDL (natLDL), as titers against oxLDL or as differences between binding to oxLDL and natLDL showed significant differences among groups of coronary heart disease (CHD) patients with different diagnosis or treatment procedures. However, there were no differences among the groups when the results were expressed as the ratio between antibody titer against oxLDL and a standard serum (oxLDL/stand). After standardization oxLDL autoantibody test may become a useful tool for analysis of the risk for CHD.

Concordance of diet with the recommended cholesterol lowering diet in patients with coronary heart disease

Objective: The aim was to examine the concordance of diet with the recommended cholesterol lowering diet in Coronary Heart Disease (CHD) patients receiving usual care.Design: CHD patients were selected for a survey from hospital records at least six months after hospitalization. Four patient groups divided according to the severity of disease were examined in cross-sectional setting. Food records and fatty acid composition of serum lipids were used to assess dietary intake.Subjects: The study population consisted of 109 patients with coronary bypass grafting, 106 patients with balloon angioplasty, 101 patients with acute myocardial infarction and 99 patients with acute myocardial ischemia.Results: Concordance of the diet with the cholesterol lowering diet was similar in the patient groups. One third of the patients achieved the recommended fat intake and only one fourth achieved the recommended saturated fat intake. Concordance was better in the patients who also used lipid lowering drugs, but previous myocardial infarction did not affect dietary intake of fat and saturated fat. Diabetic or obese patients tended to have a higher intake of saturated fat. Myristic acid in cholesterol esters, triglycerides and phospholipids and also palmitic and linoleic acids in triglycerides were markers of dietary saturated fat intake.Conclusions: Concordance of the diet with the recommended cholesterol lowering diet in CHD patients was moderate. Concordance was not affected by disease severity or previous myocardial infarction and was slightly worse in CHD patients who had diabetes or were obese or did not use lipid lowering drugs.Sponsorship: The Aarne and Aili Turunen Foundation; The Finnish Cultural Foundation; The Finnish Cultural Foundation of Northern Savo; and The Finnish Foundation for Cardiovascular Research.