Serum Cholesterol Ester Fatty Acid Research Articles

Evaluation of the serum cholesterol ester fatty acid composition in the elderly with subclinical atherosclerosis

Objective To investigate serum levels of cholesterol ester fatty acids in elderly patients with subclinical atherosclerosis (AS), in order to provide supportive laboratory data for early prevention of AS. Methods A retrospective study was undertaken on 180 elderly volunteers (age ≥60 years) who had received regular health checkups at Beijing Hospital in 2013, including 92 subclinical AS patients (the subclinical AS group) with carotid intima-media thickness (cIMT) greater than 1 mm and 88 healthy subjects (the control group). Venous blood samples were taken. Liquid chromatography tandem mass spectrometry was used to determine eleven serum cholesterol ester fatty acids, and enzyme activities of desaturases and elongases were estimated from product-to-precursor ratios. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein AI (ApoAI), ApoB, high sensitivity C-reactive protein (hsCRP) and other biochemical indicators were analyzed with automatic biochemistry analyzers and the results were analyzed with independent sample t-test, nonparametric test and logistic regression. Results Compared with the control group, age, TC, LDL-C, ApoB, serum CE16: 1 and Δ9-desaturase were higher, and serum CE22: 6 was lower in the subclinical AS group (P<0.05). After adjustment for confounding factors such as age, gender, body mass index, TC, TG, HDL-C, and LDL-C, the odds ratio of serum CE22: 6 was 0.29 (95%CI: 0.11-0.78, Wald χ2: 6.009, P<0.05), compared with the highest quartile and the lowest quartile. However, no significant difference was found in serum CE16: 1 and Δ9-desaturase. Spearman partial correlation analysis was used to analyze the relationship between CE22: 6 and the cardiovascular disease risk index and revealed that CE22: 6 was negatively correlated with Apo A, TC and HDL-C (r=-0.166, -0.149 and -0.194, respectively, each P<0.05), while no significant correlation with other indicators was found. Conclusions Serum CE22: 6 may play a protective role in subclinical AS patients. A balanced intake of fatty acids is helpful for prevention of AS in elderly people. Key words: Fatty acids; Docosahexaenoic acid ester; Atherosclerosis

Childhood Serum Fatty Acid Quality Is Associated with Adult Carotid Artery Intima Media Thickness in Women but Not in Men

AbstractChildhood nutrition may play a role in the development of cardiovascular disease risk in adulthood. We examined the links between childhood dietary fatty acid quality and adult subclinical atherosclerosis in a cohort of 374 males and 449 females, aged 3–18 y at baseline in 1980, followed for 27 y. Serum cholesterol ester fatty acid (CEFA) percentages were analyzed as markers of dietary fatty acid intake. Adulthood carotid artery intima media thickness (cIMT, μm), adjusted for childhood and adulthood lipid and nonlipid risk markers, was used as the outcome. In women, after adjustment for age and childhood nonlipid risk markers, the childhood saturated CEFA (B = 11.3; P = 0.011), monounsaturated CEFA (B = 2.5; P = 0.025), and n3 (ω3) polyunsaturated CEFA (B = 16.2; P = 0.035) percentages were directly associated with adult cIMT. In contrast, the n6 (ω6) polyunsaturated CEFA percentage was negatively associated with cIMT (B = −2.3; P = 0.008). Similar relationships were observed between childhood dietary intake data and adult cIMT. In men, these associations were generally weak and nonsignificant (P > 0.05) after controlling for confounders. These longitudinal data suggest that fat quality as reflected in the serum cholesterol ester fraction in childhood is associated with adult cIMT in women.

Childhood serum cholesterol ester fatty acids are associated with blood pressure 27 y later in the Cardiovascular Risk in Young Finns Study

In adults, dietary fatty acids (FAs) modify blood pressure (BP), but it is not known whether childhood FA quality is associated with adulthood BP. The purpose of the study was to investigate links between childhood serum cholesterol ester fatty acid (CEFA) proportions and adulthood systolic blood pressure (SBP) and diastolic blood pressure (DBP). We examined a cohort of 803 boys and girls (aged 3-18 y at baseline in 1980 and followed for 27 y) by using regression models adjusted for the known risk factors of BP. CEFAs were analyzed as markers of dietary FA intake. In men, serum SFA (B = 2.97, P < 0.001 for SBP; B = 1.48, P = 0.015 for DBP), MUFA (B = 0.61, P = 0.001 for SBP; B = 0.27, P = 0.078 for DBP), and omega-3 (n-3) PUFA (B = 5.50, P < 0.001 for SBP; B = 2.47, P = 0.015 for DBP) proportions, which were derived mainly from animal fats in this population, were positively associated with BP, whereas the omega-6 (n-6) PUFA proportion, which was derived mainly from vegetable oils and margarines, was negatively associated with BP (B = -0.56, P < 0.001 for SBP; B = -0.27, P < 0.018 for DBP). Serum cholesterol ester SFA and PUFA associations were supported by dietary intake data. In women, the associations between CEFA proportions and BP were weaker [for SBP: B = 0.36, P = 0.638 (NS) for SFA; B = 0.44, P = 0.019 for MUFA; B = 1.18, P = 0.376 (NS) for n-3 PUFA; and B = -0.33, P = 0.023 for n-6 PUFA]. Our findings suggest that fat quality as reflected in the serum cholesterol ester fraction in childhood is independently associated with adulthood BP particularly in men but also, to some extent, in women.

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 alpha-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.

Fatty acid composition of serum cholesterol esters as a reflector of low‐saturated‐fat, low‐cholesterol diet in young children: the STRIP project

STRIP (the Special Turku coronary Risk factor Intervention Project) is an ongoing intervention trial which aims at a permanent reduction in the intake of saturated fat and cholesterol starting in childhood. A total of 75 intervention and 63 control children was studied consecutively at the ages of 7 and 13 mo, and 2, 3 and 5 y to evaluate the influence of such intervention on serum cholesterol ester (CE) fatty acid composition, a widely used biomarker of fatty acid intake. Analysis of 4‐d food records showed that total intake of fat and of saturated fat increased with age in both groups of children but was constantly lower in intervention than in control children, e.g. at the age of 5 y the mean intakes of total fat and of saturated fatty acids were 31.1 E% and 33.9 E% and 12.1 E% and 14.6E% in intervention and control children, respectively (p = 0.009 and 0.0001, respectively). Serum CE fatty acid compositions did not differ between the 2 groups at any age; the mean proportion of CE linoleic acid was 52.4% and 52.0% in 5‐y‐old intervention and control children, respectively. Correlation analysis showed, however, that the percentage of linoleic acid and of polyunsaturated fatty acids in CE reflected well the respective dietary intakes (r= 0.36; p = 0.0001 for both coefficients).In conclusion, CE fatty acid composition did not differ between the intervention and control groups, whereas CE linoleic and total polyunsaturated fatty acids reflected well the differences in their intakes at the individual level.

Serum cholesterol ester fatty acids in 7‐ and 13‐month‐old children in a prospective randomized trial of a low‐saturated fat, low‐cholesterol diet: the STRIP baby project

To evaluate changes that occur in serum cholesterol ester fatty acid composition during the transition from typical infant feeding to a more adult type of nutrition, this study compared the effects on serum cholesterol ester fatty acids of breast milk or formula at the age of 7 mo with effects caused by 6‐mo dietary intervention in 137 children. The intervention [Special Turku coronary Risk factor Intervention Project for children (STRIP baby project)] aimed at a reduction of saturated fat intake to 10% of energy after the age of 1 y without purposefully influencing total fat intake. Nutrient intakes were calculated from 3‐d food records. At the age of 7 mo, i.e. before dietary education began, milk type markedly influenced dietary and serum cholesterol ester fatty acid composition (mean serum cholesterol ester 16:0 in breastfed vs formula‐fed infants, 13.7% vs 12.0%, respectively, p &lt; 0.001; serum cholesterol ester 18:2n‐6 50.6% vs 57.6%, p &lt; 0.001). At the age of 13 mo the calculated fat intake of the intervention and control children differed markedly but serum cholesterol ester fatty acid compositions in all children resembled closely those measured in 7‐mo‐old breastfed infants, e.g. at the age of 13 mo the relative proportions of 18:2n‐6 were 49.9% and 51.1% in previously formula‐fed intervention and control children, respectively, and 50.3% and 50.1% in previously breastfed intervention and control children, respectively. In conclusion, serum cholesterol ester fatty acid composition reflected differences in dietary fat quality (breast milk or formula) at the age of 7 mo, whereas dietary intervention as applied in the STRIP baby project had only a minimal effect. □Cholesterol esters, dietary intervention, fatty acids, infant feeding

Serum cholesterol ester fatty acids in 7- and 13-month-old children in a prospective randomized trial of a low-saturated fat, low-cholesterol diet: the STRIP baby project

To evaluate changes that occur in serum cholesterol ester fatty acid composition during the transition from typical infant feeding to a more adult type of nutrition, this study compared the effects on serum cholesterol ester fatty acids of breast milk or formula at the age of 7 mo with effects caused by 6-mo dietary intervention in 137 children. The intervention [Special Turku coronary Risk factor Intervention Project for children (STRIP baby project)] aimed at a reduction of saturated fat intake to 10% of energy after the age of 1 y without purposefully influencing total fat intake. Nutrient intakes were calculated from 3-d food records. At the age of 7 mo, i.e. before dietary education began, milk type markedly influenced dietary and serum cholesterol ester fatty acid composition (mean serum cholesterol ester 16:0 in breastfed vs formula-fed infants, 13.7% vs 12.0%, respectively, p < 0.001; serum cholesterol ester 18:2n-6 50.6% vs 57.6%, p < 0.001). At the age of 13 mo the calculated fat intake of the intervention and control children differed markedly but serum cholesterol ester fatty acid compositions in all children resembled closely those measured in 7-mo-old breastfed infants, e.g. at the age of 13 mo the relative proportions of 18:2n-6 were 49.9% and 51.1% in previously formula-fed intervention and control children, respectively, and 50.3% and 50.1% in previously breastfed intervention and control children, respectively. In conclusion, serum cholesterol ester fatty acid composition reflected differences in dietary fat quality (breast milk or formula) at the age of 7 mo, whereas dietary intervention as applied in the STRIP baby project had only a minimal effect.

Milk type during mixed feeding: Contribution to serum cholesterol ester fatty acids in late infancy

Objective: To evaluate the contribution of the type of milk on serum cholesterol ester fatty acids in infants receiving mixed feeding, we analyzed 3-day dietary records and serum cholesterol ester fatty acid composition of 397 seven-month-old infants. Study design: The infants received, in addition to solid food, only one type of milk: human milk (n = 218), a ready-to-use liquid formula (n = 139), a powdered formula (n = 33), or soy formula (n = 7). Results: Mean fat intakes were low and varied from 28% to 31% of energy; the milks provided 43% to 64% of the fat. The mean polyunsaturated/saturated fat ratios of solid foods were from 0.52 to 0.63 and of milks from 0.20 to 0.45. Breast-fed infants' relative serum linoleic acid (18:2n-6) concentration was low (51.2%), whereas infants fed liquid formula had low serum oleic acid (18:1n-9) in accordance with low oleic acid content in that formula. The breast-fed infants had markedly higher serum concentrations of arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) than the infants fed any of the formulas. Conclusion: The typical fatty acid patterns of breast- or formula-fed infants were still evident in 7-month-old infants who already received 60% to 70% of their energy from solid food. Marked differences were seen also in the relative concentrations of docosahexaenoic acid and arachidonic acid despite their small contribution in cholesterol esters. (J Pediatr 1997;130:110-6)

The serum cholesterol ester fatty acid composition but not the serum concentration of alpha tocopherol predicts the development of myocardial infarction in 50-year-old men: 19 years follow-up

A low serum tocopherol concentration and a low proportion of linoleic acid in plasma cholesterol esters have been reported to be associated with coronary heart disease. This study was undertaken to evaluate the predictive importance of the serum cholesterol ester fatty acid composition and serum tocopherol concentration in addition to established risk factors for myocardial infarction. The study comprised 2322 fifty-year-old men who participated in a health survey in 1970–1973 regarding risk factors for coronary heart disease. The proportions of myristic, palmitic, palmitoleic, and dihomogammalinolenic acid were significantly higher in 1970–1973 in subjects who suffered myocardial infarction during the following 19 years, while the proportion of linoleic acid was lower, than in those who remained healthy. Serum tocopherol did not differ significantly between the groups. LDL HDL ratio, systolic blood pressure, and arachidonic acid/dihomogammalinolenic acid ratio were significant independent discriminators between cases and controls in a stepwise logistic regression analysis. This study suggests that middle-aged men who later develop a myocardial infarction are characterized not only by conventional risk factors but also by an altered fatty acid composition of serum cholesterol esters, with a low arachidonic to dihomogammalinolenic acid ratio, indicating reduced Δ 5 desaturase activity. This may imply that changes in the quality of dietary fat intake, or an altered capacity to metabolize fatty acids in the body, could precede the development of coronary heart disease.

Lipoprotein composition and serum cholesterol ester fatty acids in nonwesternized melanesians

In this study, the relationships between dietary fat [as measured by serum cholesterol ester fatty acids (CE-FA)], age, smoking, body mass index, and serum lipids were analyzed in 151 subsistence horticulturalists, aged 20-86 yr, from Kitava, Trobriand Islands, Papua New Guinea. Their diet consists of tubers, fruit, coconut, fish, and vegetables with a negligible influence of western food and alcohol. Total fat intake is low [21% of energy (en%)], while saturated fat intake from coconuts is high (17 en%, mainly lauric and myristic acid). In multivariate analysis, 11-43% of the variation of the serum lipoprotein composition was explained by CE-FA, age, and smoking habits. The proportion of CE20:5n-3 explained much of the variation of triglycerides (TG, negative relation) and high density lipoprotein-cholesterol (HDL-C, positive) in both sexes and serum apolipoprotein A1 (ApoA1, positive) in the males. CE16:0 was positively related to TG and negatively related to HDL-C and ApoA1 in both sexes, and in males it related negatively to total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C). In males, negative relationships were present between CE18:2n-6 and TC and between CE14:0 and serum lipoprotein(a). Smoking was independently associated with lower ApoA1 in both sexes and with lower HDL-C and higher TG, TC, LDL-C, and apolipoprotein B in males. In conclusion, marine n-3 fatty acids and linoleic acid showed the same potentially beneficial relationships with lipoproteins and apolipoproteins as in western populations. The relations of palmitic acid to serum lipids may be explained in terms of endogenous fat synthesis at a low-fat intake, rather than reflecting its relative intake.

The risk to develop NIDDM is related to the fatty acid composition of the serum cholesterol esters.

This investigation was undertaken to study whether the risk to develop non-insulin-dependent diabetes mellitus (NIDDM) among 50-year-old men during a 10-year follow-up period was related to the fatty acid composition of their serum cholesterol esters. There were highly significant differences in the initial health survey between the fatty acid composition in serum in subjects who remained normoglycemic (n = 1,753) and in those who later developed NIDDM (n = 75). The main differences were that the latter had higher proportions of saturated fatty acids and palmitoleic acid (16:1 omega-7), a low proportion of linoleic acid (18:2 omega-6), and a relatively high content of gamma-linolenic (18:3 omega-6) and dihomo-gamma-linolenic (20:3 omega-6) acids in the serum cholesterol esters. The picture was similar also after adjusting for differences in body mass index. In a logistic model, a high proportion of dihomo-gamma-linolenic acid remained a significant contributor to the development of diabetes, along with the height of the insulin index, the blood glucose concentration at 60 min, and the fasting insulin concentration. The increased risk to develop NIDDM related to the serum cholesterol ester fatty acid composition may be mediated by diet and/or genetic factors.

The Partial Ileal Bypass Operation Does Not Cause Essential Fatty Acid Deficiency

Recent studies have indicated that ileal resection may lead to essential fatty acid deficiency, as demonstrated by plasma fatty acid composition. In the present study the serum cholesterol ester fatty acid composition was determined in patients who had undergone a partial ileal bypass operation several years earlier. The mean length of ileal exclusion was 2.0 m (range, 1.4-2.5 m). The patients with ileal bypass had severe bile acid malabsorption and slight fat malabsorption (fecal fat, 16 g/day). The fatty acid composition of serum cholesterol esters in the patients with ileal exclusion was identical with that of matched controls; for example, linoleic acid comprised 58% of the C14-18 fatty acids in the control patients and 61% in the patients with ileal bypass. It is concluded that exclusion of the distal third of a healthy small bowel does not cause essential fatty acid deficiency.

Comparison of arterial lesions and serum lipids in spider and rhesus monkeys on an egg and butter diet

Serum and aortic lipids and atherosclerotic lesions were studied in five spider monkeys (Ateles sp.) and three rhesus monkeys ( Macaca mulatta) after changing from a commercial chow diet to a high fat (40% of calories), high cholesterol (1 mg/cal), semisynthetic diet containing egg yolk and butter. There was a large species difference in response of serum cholesterol. After 12 weeks on the diet the mean elevation of serum cholesterol was 285 mg/100 ml for the rhesus and 17 mg/100 ml for the spider monkeys. Changes in serum cholesterol ester fatty acid patterns were also very much greater for the rhesus than for the spider monkey. Aortas and coronary arteries of the rhesus were extensively involved with sudanophilic lesions. The cholesterol and cholesterol ester content of the aortic intima was much greater in the rhesus than in the spider monkey. The proportional contribution of aortic cholesterol oleate was greater in rhesus than spider monkeys and the palmitate was lower. There were only a few sudanophilic lesions in the coronary arteries of the spider monkeys. The coronary arteries of one older rhesus monkey were extensively involved with fibrous lesions. There was no appreciable difference between species in the histologic appearance of the sudanophilic lesions.

Cholesterol ester and phospholipid composition of normal aortas and of atherosclerotic lesions in children

Gas chromatographic techniques have been used to study the lipid composition of children's arteries over the first decade of life. Children's aortas were separated into intima and media and, where present, into intimal fatty streak lesions and media underlying such lesions, and the level of cholesterol ester and of phospholipid and the fatty acid composition of these fractions in these various portions of the aortas was determined. The ester cholesterol concentration of the normal intima, but not of the media, increased with age. The ester cholesterol concentration of the fatty streak lesions exceeded that of the normal intima and also increased with age. No changes with age in phospholipid content for normal intima or media or for the intimal lesion were observed. The cholesterol ester fatty acid composition of the normal intima and of the media was similar to that of the lesions studied, and all tissues manifested a change in composition with age; cholesterol linoleate increasing and cholesterol palmitate decreasing during the first decade. These age changes for the aortic fractions were shown to resemble changes with age in the serum cholesterol ester fatty acids. The phospholipid fatty acid pattern of normal intima and media resembled those of the lesion but no change with age in phospholipid fatty acid pattern was found. No correspondence of the aortic phospholipid pattern with the serum pattern was demonstrated. These data are consistent with the view that arterial cholesterol ester, but not phospholipid, in both the normal intima and in the early fatty streak lesion in children arises initially from serum.

Serum and Aortic Lipids in Rabbits Fed Cholesterol and Linoleic Acid Stereoisomers

Rabbits fed 1 g of cholesterol and 6 g of elaidinized linoleic acid (a mixture of linoelaidic stereoisomers) daily for 84 days showed no higher concentration of free cholesterol, cholesterol ester, triglyceride, phosphatidyl ethanolamine, phosphatidyl serine, lecithin, sphingomyelin or other lipid fractions in their serum than did control rabbits fed 1 g cholesterol and 6 g linoleic acid for a similar period. In the rabbits fed the elaidinized linoleic acid the concentration of trans isomer after 84 days was 13.2 ± 11.3% in the serum cholesterol ester fatty acids and 11.3 ± 8.2% in the triglyceride fatty acids, whereas it was usually less than 2.5% in the phospholipid fatty acids. The rabbits fed elaidinized linoleic acid showed little, or no more, atherosclerosis of the aortic arch, no more atherosclerosis in the thoracic and abdominal aorta, and only a slightly higher cholesterol content in their aortas than did those rabbits fed natural linoleic acid and cholesterol. The relationship of these results to those of similar experiments in which supplements of elaidinized oleic acid or olive oil were fed with cholesterol to rabbits is discussed.

Relation of age and race to serum cholesterol ester fatty acid composition.

SummaryThe serum CEFA and cholesterol level of children (6-10 years old) and older subjects (60-87 years old) of both negro and white races have been compared. Children of both races had significantly less oleic acid and significantly more linoleic acid in their serum CEFA fraction than older subjects. Arachidonic acid did not show significant changes with increasing age. Negro and white subjects of the same age group did not show significant differences in CEFA spectrum. Also, children had a significantly lower total blood cholesterol level than older individuals. The significance of these findings as related to atherosclerosis is discussed.

Serum lipid analyses in rats fed natural and hydrogenated cottonseed oil with cholesterol and cholate.

Summary1. Dietary cholate with cholesterol added to natural and hydrogenated cottonseed oil raised serum cholesterol and phospholipid. This effect was augmented with saturated fat. Dietary lipid saturation or cholate alone had no effect on serum cholesterol. 2. C/PL ratio was elevated only when both dietary cholate and cholesterol were added to hydrogenated fat. 3. In the rat, highly saturated fat (I# 43) fed with cholesterol reverses the Alpha to Beta LP ratio with Beta LP becoming dominant. Combination of dietary cholate with cholesterol permits reversal of Alpha to Beta LP with moderate (I# 78) or no hydrogenation (I# 107) of dietary fat. 4. Serum cholesterol ester fatty acid composition changes with greater saturation of dietary fat and added cholate and cholesterol. High oleic acid levels were noted in serum cholesterol ester fraction of rats fed saturated fat (I# 78) with cholate and cholesterol.