C-reactive protein, dietary n-3 fatty acids, and the extent of coronary artery disease.

The acute-phase reactant C-reactive protein (CRP) has emerged as an independent risk factor for coronary artery disease. Experimental and clinical studies provide evidence of anti-inflammatory effects of n-3 polyunsaturated fatty acids (PUFA) derived from fish. We have studied the effect of marine n-3 PUFA on CRP levels in 269 patients referred for coronary angiography because of clinical suspicion of coronary artery disease. All patients filled out a food questionnaire regarding fish intake. The n-3 PUFA content of granulocyte membranes was determined and the concentration of CRP in serum was measured using a highly sensitive assay. The results were related to angiographic findings. CRP was significantly higher in patients with significant coronary stenoses than in those with no significant angiographic changes (p <0.001), but the CRP levels were not associated with the number of diseased vessels. Subjects with CRP levels in the lower quartile had a significantly higher content of docosahexaenoic acid (DHA) in granulocytes than subjects with CRP levels in the upper quartile (p = 0.02), and in a multivariate linear regression analysis, DHA was independently correlated to CRP (R(2) = 0.179; p = 0.003). The inverse correlation between CRP and DHA may reflect an anti-inflammatory effect of DHA in patients with stable coronary artery disease and suggest a novel mechanism by which fish consumption may decrease the risk of coronary artery disease.     

Serum N-3 polyunsaturated fatty acid levels correlate with the extent of coronary plaques and calcifications in patients with acute myocardial infarction

BACKGROUND: The relationship between serum fatty acid levels and the extent of coronary plaques and calcification was examined in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: The serum levels of the n-3 polyunsaturated fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) and the n-6 polyunsaturated fatty acids (arachidonic acid (AA) and dihomo-gamma-linolenic acid (DGLA)) were determined using gas chromatography on admission of 95 consecutive patients with their first AMI and 17 controls. Using multidetector-row computed tomography, soft plaques and calcification lesions were scored according to the extent of coronary involvement. Serum logarithmic transformed (log) EPA and logDHA levels were inversely correlated with soft plaque scores (r=-0.546, p<0.0001 and r=-0.377, p<0.0001, respectively). Serum logAA and logDGLA levels were not significantly correlated with soft plaque scores. Serum logEPA and logDHA levels were significantly, but weakly, correlated with calcification scores. Multivariate analysis with clinical characteristics and risk factors selected serum n-3 polyunsaturated fatty acid levels as independent factors associated with the extent of coronary soft plaques. CONCLUSION: The present study demonstrates a significant correlation between serum n-3 polyunsaturated fatty acid levels and the extent of coronary soft plaques and calcification in AMI patients.     

Relation of long chain n-3 polyunsaturated fatty acid intake to serum high density lipoprotein cholesterol among Japanese men in Japan and Japanese-American men in Hawaii: the INTERLIPID study

Epidemiologic evidence shows an inverse relationship between fish consumption and coronary heart disease (CHD) mortality. Associations between dietary intake of long chain n-3 polyunsaturated fatty acids (PUFA) and serum high density lipoprotein (HDL) cholesterol concentration are unknown. In this study, the association between n-3 PUFA (eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA)) intake and serum HDL cholesterol among Japanese men and women in Japan and Hawaii was examined. The study population consisted of Japanese ancestries from five research centers of the International Study of Macronutrients and Blood Pressure (INTERMAP) study, in Japan and Hawaii (672 men and 676 women), surveyed between 1996 and 1998. Four 24-h dietary recalls and one set of serum lipid measurements were performed. For men, n-3 PUFA intake and HDL cholesterol were higher in Japan than in Hawaii (n-3 PUFA: 1.32 g/day versus 0.47 g/day, p<0.001). For women, n-3 PUFA intake was higher in Japan than in Hawaii (p<0.001) but HDL cholesterol was not significantly different (p=0.752). After adjustment for age, body mass index, physical activity, number of cigarettes per day, alcohol intake, and hormone replacement therapy (for women), n-3 PUFA intake was positively associated with serum HDL cholesterol in men (4.6 mg/dl higher HDL cholesterol with 1%kcal higher n-3 PUFA intake, p=0.011). This association was not observed in women. This positive association of dietary n-3 PUFA with serum HDL cholesterol may partially explain the low mortality from CHD among Japanese men.     

Aberrant serum polyunsaturated fatty acids profile is relevant with acute coronary syndrome

Although a robust relationship between aberrant serum polyunsaturated fatty acids (PUFAs) profile and coronary artery disease (CAD) has been reported, the details concerning the association between aberrant PUFAs profile and clinical feature of CAD are not fully discovered. Therefore, we investigated the relationship between serum PUFAs and clinical profiles in CAD patients. We classified 595 consecutive CAD patients, who underwent coronary angiography into 3 groups according to the clinical profiles of CAD (group A: early phase ACS, n = 96; group B: stable CAD with previous history of ACS, n = 259; group C: stable CAD without previous history of ACS, n = 240) and measured serum n-3 [eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)] and n-6 [arachidonic acid (AA)] PUFAs. Serum EPA, DHA, and EPA/AA ratio were significantly low in the order of group A < B < C [EPA; 48.1 (34.1–60.3) μg/ml, 61.7 (41.2–94.5) μg/ml, and 74.4 (52.7–104.9) μg/ml, DHA; 113.1 (92.8–135.1) μg/ml, 125.8 (100.4–167.2) μg/ml, and 140.1 (114.7–177.0) μg/ml, EPA/AA ratio; 0.31 (0.22–0.45), 0.39 (0.26–0.62), and 0.44 (0.31–0.69), medians with interquartile range, p < 0.01]. Multiple regression analysis revealed that EPA (p = 0.009) and EPA/AA ratio (p = 0.023), but not DHA and DHA/AA ratio, were negatively associated with clinical profiles of ACS in CAD patients. Significant correlation was not observed between PUFAs profile and severity of coronary stenosis. Low serum EPA and EPA/AA ratio correlates with clinical profiles of ACS in patients with CAD, regardless of the extent and severity of coronary artery stenosis.     

Relation of whole blood n-3 fatty acid levels to exercise parameters in patients with stable coronary artery disease (from the heart and soul study)

Dietary intake of n-3 polyunsaturated fatty acids is associated with a lower incidence of cardiovascular events. Mechanisms underlying this association are poorly understood but may include beneficial effects on physical conditioning and vagal tone. We investigated the association of n-3 fatty acid levels to exercise parameters in 992 subjects with stable coronary artery disease. Cross-sectional associations of heart rate recovery time, treadmill exercise capacity, and exercise time with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) levels were evaluated in multivariable linear and logistic regression models adjusted for demographics, cardiovascular risk factors, co-morbidities, self-reported physical activity, medication use, and left ventricular function. After multivariable adjustment, n-3 fatty acid levels (DHA + EPA) were strongly associated with heart rate recovery (beta 2.1, p = 0.003), exercise capacity (beta 0.8, p <0.0001), and exercise time (beta 0.9, p <0.0001). Increasing levels of (DHA + EPA) were also associated with decreased risk of impaired heart rate recovery (odds ratio 0.8, p = 0.004) and exercise time (odds ratio 0.7, p = 0.01) and trended toward significance for exercise capacity (odds ratio 0.8, p = 0.07). These associations were not modified by demographics, body mass index, smoking, co-morbid conditions, statin use, or β-blocker use (p for interaction >0.1 for all comparisons). In conclusion, an independent association exists between n-3 fatty acid levels and important exercise parameters in patients with stable coronary artery disease. These findings support the hypothesis that n-3 fatty acids may increase vagal tone and physical conditioning.     

High concentrations of omega-3 fatty acids are associated with the development of atrial fibrillation in the Japanese population

The favorable effect of fish oils rich in n-3 polyunsaturated fatty acids (PUFAs) on the development of atrial fibrillation (AF) is controversial. The relationship between the serum concentrations of n-3 PUFAs and the incidence of AF is unclear; therefore, in the present study, we aimed to elucidate this relationship. We evaluated the serum concentrations of n-3 PUFAs in 110 patients with AF, 46 patients with ischemic heart disease (IHD) and no AF, and 36 healthy volunteers. Thirty-six patients had a history of IHD (IHD-AF group) and 74 did not (L-AF group). The eicosapentaenoic acid (EPA) levels in the L-AF group were higher than those in the IHD-AF and control groups (117 ± 64, 76 ± 30, and 68 ± 23 μg/ml, respectively); the docosahexaenoic acid (DHA) levels showed the same pattern (170 ± 50, 127 ± 27, and 126 ± 35 μg/ml, respectively). In both the L-AF and IHD-AF groups, the EPA levels in patients with persistent and permanent AF were higher than those in patients with paroxysmal AF (L-AF 131 ± 74 vs. 105 ± 51 μg/ml; IHD-AF 82 ± 28 vs 70 ± 33 μg/ml). Multivariate analysis showed that cases of AF were associated with higher levels of EPA but not DHA. In this Japanese population study, the EPA and DHA levels in patients with L-AF were higher than those in normal subjects. In particular, the EPA level was associated with the incidence of AF. These findings suggest that an excess of EPA might be a precipitating factor of AF.     

Are omega-3 fatty acids the most important nutritional modulators of coronary heart disease risk?

With each passing year, the evidence linking an increased risk for coronary heart disease (CHD) death with a chronic dietary deficiency in long-chain omega-3 (n-3) fatty acids (FAs) grows stronger. Recently, a federally mandated evidence-based review in the United States concluded that n-3 FAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have clear cardioprotective effects, and national and international expert panels and health organizations have begun to call for increased EPA and DHA intakes. Consumption of between 450 and 1000 mg/d is recommended for those without and with known CHD, respectively. Based on animal and isolated cell studies, these FAs were presumed to have antiarrhythmic effects. The first direct evidence for this in humans was recently published, as were new data linking low n-3 FA intakes with risk for developing atrial fibrillation. The strength of the n-3 story has now led to a proposal that blood levels of EPA plus DHA be considered a new, modifiable, and clinically relevant risk factor for death from CHD.     

冠心病患者血清脂联素和高敏C反应蛋白的观察

目的探讨冠心病患者血清脂联素和高敏C反应蛋白(hs-CRP)水平的相关性。方法可疑冠心病患者83例行冠状动脉造影,确诊冠心病患者65例,分为稳定性心绞痛组(SAP组,21例)和急性冠状动脉综合征组(ACS组,44例),冠状动脉造影正常者作为对照组(18例)。测定各组患者血清脂联素和hs-CRP水平。结果ACS组患者血清脂联素对数水平较对照组和SAP组明显降低(P<0.05);ACS组患者hs-CRP水平高于SAP组和对照组(P<0.05)。线性相关分析表明,血清脂联素对数与hs-CRP水平呈负相关(r=-0.25,P<0.05)。结论血清脂联素与hs-CRP相互作用可能共同参与了冠状动脉粥样硬化的发生与发展。     

Association of circulating levels of leptin and adiponectin with metabolic syndrome and coronary heart disease in patients with various coronary risk factors

The aim of this study was to investigate the associations of adiponectin and leptin with metabolic syndrome (MetS) and coronary heart disease (CHD) in patients with various coronary risk factors. We determined serum adiponectin, leptin, and metabolic syndrome components in 104 patients (59 men and 45 women; aged 40-86 years) with various coronary risk factors at a cardiovascular out-patient clinic. Natural logarithmic transformed (ln) leptin was lower in men and smokers, and positively correlated with body mass index (BMI) (r = 0.59, P < 0.0001), waist circumference (r = 0.60, P < 0.0001), and homeostasis model assessment of insulin resistance (HOMA-IR) levels (r = 0.24, P < 0.02). Ln adiponectin was higher in women and nonsmokers, and was correlated with age and high-density lipoprotein cholesterol (HDL-C). Patients with MetS (n = 69) had significantly higher BMI, HOMA-IR, and ln leptin and lower ln adiponectin than those without Mets (Ln leptin, 2.14 ± 0.08 versus 1.30 ± 0.11; Ln adiponectin, 2.29 ± 0.06 versus 2.54 ± 0.09). In contrast, patients with coronary heart disease (CHD: n = 40) had significantly lower serum ln adiponectin concentrations than non-CHD patients (n = 64) (1.79 ± 0.12 versus 1.91 ± 0.10) as well as lower HDL-C and a higher smoking percentage. Consistent results were obtained by multivariate analyses. In conclusion, this study disclosed factors associated with the increase in serum leptin and adiponectin. Serum levels of leptin may be associated positively with MetS, whereas adiponectin levels are associated negatively with MetS and CHD, even in patients with various coronary risk factors.     

Serum long-chain n-3 polyunsaturated fatty acids and aortic calcification in middle-aged men: The population-based cross-sectional ERA-JUMP study

Background and aimFew studies have examined the association of long-chain n-3 polyunsaturated fatty acids (LCn-3PUFAs) with the measures of atherosclerosis in the general population. This study aimed to examine the relationship of total LCn-3PUFAs, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) with aortic calcification.Methods and resultsIn a multiethnic population-based cross-sectional study of 998 asymptomatic men aged 40–49 years (300 US-White, 101 US-Black, 287 Japanese American, and 310 Japanese in Japan), we examined the relationship of serum LCn-3PUFAs to aortic calcification (measured by electron-beam computed tomography and quantified using the Agatston method) using Tobit regression and ordinal logistic regression after adjusting for potential confounders. Overall 56.5% participants had an aortic calcification score (AoCaS) > 0. The means (SD) of total LCn-3PUFAs, EPA, and DHA were 5.8% (3.3%), 1.4% (1.3%), and 3.7% (2.1%), respectively. In multivariable-adjusted Tobit regression, a 1-SD increase in total LCn-3PUFAs, EPA, and DHA was associated with 29% (95% CI = 0.51, 1.00), 9% (95% CI = 0.68, 1.23), and 35% (95% CI = 0.46, 0.91) lower AoCaS, respectively. Results were similar in ordinal logistic regression analysis. There was no significant interaction between race/ethnicity and total LCn–3PUFAs, EPA or DHA on aortic calcification.ConclusionsThis study showed the significant inverse association of LCn-3PUFAs with aortic calcification independent of conventional cardiovascular risk factors among men in the general population. This association appeared to be driven by DHA but not EPA.     

Association of adiponectin and resistin with adipose tissue compartments, insulin resistance and dyslipidaemia

AIM: In this study, we investigated the association of plasma adiponectin and resistin concentrations with adipose tissue compartments in 41 free-living men with a wide range of body mass index (22-35 kg/m(2)). METHODS: Using enzyme immunoassays, plasma adiponectin and resistin were measured. Intraperitoneal, retroperitoneal, subcutaneous abdominal and posterior subcutaneous abdominal adipose tissue masses (IPATM, RPATM, SAATM and PSAATM, respectively) were determined using magnetic resonance imaging. Total adipose tissue mass (TATM) was measured using bioelectrical impedance. Insulin resistance was estimated with the help of homeostasis model assessment (HOMA) score. RESULTS: In univariate regression, plasma adiponectin levels were inversely related to IPATM (r = -0.389, p < 0.05), SAATM (r = -0.500, p < 0.001), PSAATM (r = -0.502, p < 0.001), anterior SAATM (r = -0.422, p < 0.01) and TATM (r = -0.421, p < 0.01). In multiple regression models, adiponectin was chiefly correlated with PSAATM. Plasma adiponectin concentrations were also inversely correlated with HOMA score (r = -0.540, p < 0.001) and triglyceride (r = -0.632, p < 0.001), and positively correlated with high-density lipoprotein cholesterol (r = 0.508, p < 0.001). There were no significant correlations between resistin levels and adipose tissue masses, insulin resistance or dyslipidaemia. CONCLUSIONS: In men, total body fat is significantly correlated with plasma adiponectin, but not with plasma resistin levels. Low plasma adiponectin levels appear to be chiefly determined by the accumulation of posterior subcutaneous abdominal fat mass, as opposed to intra-abdominal fat, and are strongly predictive of insulin resistance and dyslipidaemia.     

Omega-3 Polyunsaturated Fatty Acids Reduce Vascular Endothelial Growth Factor Production and Suppress Endothelial Wound Repair

Long-chain polyunsaturated omega-3 fatty acids (n-3 PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have diverse beneficial effects on cardiovascular diseases and have been used widely as supplements in reducing the risk of cardiovascular diseases. The beneficial effects are believed to be related to the anti-inflammatory and antioxidant action of n-3 PUFA. EPA and DHA can inhibit inflammatory cytokine-induced endothelial activation and reduce endothelial migration and proliferation. Revascularisation is the major therapeutic approach for end-stage cardiovascular diseases, and endothelial migration and proliferation are essential for the success of revascularisation. The aim of this study was to investigate the role of n-3 PUFAs on vascular endothelial wound repair. A scratch-wound repair assay was carried out in cultured human microvascular endothelial cells (HMEC-1) with and without different concentrations of DHA or EPA. The effect of DHA and EPA on HMEC-1 proliferation was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effect of DHA and EPA on vegf mRNA expression was detected by real-time RT-PCR and vascular endothelial growth factor (VEGF) protein secretion by enzyme-linked immunosorbent assay. DHA and EPA dose-dependently suppressed HMEC-1 cell proliferation and wound repair. DHA and EPA treatment did not induce significant HMEC-1 cell death. The treatment, however, significantly suppressed vegf mRNA expression and protein secretion in both normoxia and hypoxia culture conditions. The addition of exogenous VEGF prevented DHA- and EPA-mediated suppression of HMEC-1 cell proliferation. DHA and EPA have anti-angiogenic effect partially through vegf suppression. The use of DHA and EPA may benefit angiogenic diseases, but may have potential side effects to patients undergoing revascularisation therapy. Further studies will be required to confirm the effect of n-3 PUFAs on vascular repair.     

Intake of total omega-3 fatty acids,eicosapentaenoic acid and docosahexaenoic acid and risk of coronary heart disease in the Spanish EPIC cohort study

Background and aimsThe evidence about the benefits of omega-3 fatty acid intake on coronary heart disease (CHD) is not consistent. We thus aimed to assess the relation between dietary intake of total omega-3 fatty acids (from plant and marine foods) and marine polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on the risk of CHD in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC).Methods and resultsThe analysis included 41,091 men and women aged 20–69 years, recruited from 1992 to1996 and followed-up until December 2004. Omega-3 fatty acid intake was estimated from a validated dietary questionnaire. Only participants with definite incident CHD event were considered as cases. Cox regression models were used to assess the association between the intake of total omega-3 fatty acids, EPA or DHA and CHD. A total of 609 participants (79% men) had a definite CHD event. Mean intakes of total omega-3 fatty acids, EPA and DHA were very similar in the cases and in the cohort, both in men and women. In the multivariate adjusted model, omega-3 fatty acids, EPA and DHA were not related to incident CHD in either men or women. The hazard ratios (HR) for omega-3 were 1.23 in men (95% CI 0.94–15.9, p = 0.20); and 0.77 in women (95% CI 0.46–1.30, p = 0.76).ConclusionIn the Spanish EPIC cohort, with a relatively high intake of fish, no association was found between EPA, DHA and total omega-3 fatty acid intake and risk of CHD.     

Docosahexanoic acid and docosapentanoic acid incorporation into human platelets after 24 and 72 hours: Inhibitory effects on platelet reactivity

Short-term in vitro platelet membrane lipid enrichment studies and feeding trials of human subjects with eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) have shown a decreased reactivity in the platelet response to collagen. In this study, exogenous albumin-bound n-3 polyunsaturated fatty acids (PUFAs), namely EPA, DHA and docosapentanoic acid (DPA) were added to platelet suspensions and maintained at 22 ° C for 24 and 72 hours. Subsequently, the aggregation response to agonist stimulation and the morphological appearance of the platelets were evaluated. A significant enrichment of platelet phospholipids (PL) in n-3 fatty acids occurred upon incubation with n-3 PUFAs in vitro, which was accompanied by a decrease in the aggregation response to collagen and preservation of platelet morphology compared with non-supplemented control platelet preparations. The inhibitory effect of the n-3 PUFAs appeared to be surface mediated in the case of DHA and DPA because the platelet response to agonist returned when the fatty acids were removed by washing. The platelet aggregation response after storage at 22 ° C was also evaluated in platelet suspensions collected from healthy individuals before and after 42 days of dietary supplementation with seal oil, rich in DPA and DHA. Unlike the in vitro supplementation, in vivo modification and enrichment of platelet PLs by ingestion of seal oil did not appear to improve platelet function during storage relative to the placebo group.     

非酒精性脂肪肝患者胰岛素抵抗与脂联素基因表达的关系

目的探讨NAFLD患者胰岛素抵抗（IR）与脂肪组织脂联素基因表达的关系。方法用SYBR GreenI实时定量RT-PCR方法检测脂肪组织脂联素mRNA的表达水平，用稳态模型法计算IR指数。结果肥胖和非肥胖NAFLD患者及对照组IR指数分别为：3．0±0．8、2．8±0．9和2．0±0．6、1．2±0．5，其脂肪组织脂联素基因表达和血浆脂联素浓度较对照各组显著降低（P〈0．05），IR与脂联素基因表达（r=0．5，P〈0．05）和血浆脂联素浓度负相关（，=0．4，P〈0．05），与血清甘油三酯正相关（r=0．3，P〈0．05）。结论NAFLD患者的IR与脂肪组织脂联素基因低表达有关，脂联素基因低表达在IR和NAFLD发病中起了一定作用。     

Effect of n-3 PUFAs on arterial stiffness in patients with cardiovascular disease

Background Fish oil, rich in long-chain n-3 PUFAs, EPA and DHA, are known to reduce various risk factors for CAD1-3 . However, conclusive regarding the benefits of n-3 PUFAs on arterial stiffness, a risk factor for CAD, has not yet been established. Methods In the placebo-controlled, single-blind, prospective study, 60 subjects were randomly allocated to consume daily nutritional supplement of 3 gram capsules containing either placebo (soybean oil) or fish oil, EPA (540 mg) + DHA (360 mg) for 12 weeks. Anthropometry, pulse wave velocity (PWV) and polyunsaturated fatty acid were measured and compared before and after study therapy. Results After study therapy, PWV reduced significantly in the fish oil group compared with the placebo group (-8 ± 18cm / s vs 39 ± 19cm / s, P﹤0.05). Conclusions Fish oil shows beneficial effect on improving arterial stiffness in patients with coronary disease.     

Docosahexaenoic acid and docosapentanoic acid incorporation into human platelets after 24 and 72 hours: inhibitory effects on platelet reactivity

Short-term in vitro platelet membrane lipid enrichment studies and feeding trials of human subjects with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown a decreased reactivity in the platelet response to collagen. In this study, exogenous albumin-bound n-3 polyunsaturated fatty acids (PUFAs), namely EPA, DHA and docosapentanoic acid (DPA) were added to platelet suspensions and maintained at 22 degrees C for 24 and 72 hours. Subsequently, the aggregation response to agonist stimulation and the morphological appearance of the platelets were evaluated. A significant enrichment of platelet phospholipids (PL) in n-3 fatty acids occurred upon incubation with n-3 PUFAs in vitro, which was accompanied by a decrease in the aggregation response to collagen and preservation of platelet morphology compared with non-supplemented control platelet preparations. The inhibitory effect of the n-3 PUFAs appeared to be surface mediated in the case of DHA and DPA because the platelet response to agonist returned when the fatty acids were removed by washing. The platelet aggregation response after storage at 22 degrees C was also evaluated in platelet suspensions collected from healthy individuals before and after 42 days of dietary supplementation with seal oil, rich in DPA and DHA. Unlike the in vitro supplementation, in vivo modification and enrichment of platelet PLs by ingestion of seal oil did not appear to improve platelet function during storage relative to the placebo group.     

Blood mononuclear cells and platelets have abnormal fatty acid composition in homozygous sickle cell disease

Leukocyte adhesion to vascular endothelium contributes to vaso-occlusion and widespread organ damage in sickle cell disease (SCD). Previously, we found high expression of the adhesion molecules _M2 integrin and L-selectin in HbSS individuals with severe disease. Since membrane n-6 and n-3 polyunsaturated fatty acids modulate cell adhesion, inflammation, aggregation and vascular tone, we investigated the fatty acid composition of mononuclear cells (MNC) and platelets of HbSS patients in steady state (n=28) and racially matched, healthy HbAA controls with similar age and sex distribution living in the same environment (n=13). MNC phospholipids of the patients had lower levels of docosahexaenoic acid (DHA, p<0.01) and increased arachidonic acid (AA, p<0.005) relative to HbAA controls. Similarly, platelets from HbSS patients had less eicosapentaenoic acid (EPA, p<0.05) and more AA (p<0.05) in choline phosphoglycerides (CPG), with reduced DHA (p<0.05) in ethanolamine phosphoglycerides. Platelet CPG had lower DHA levels in SCD patients with complications compared to those without (p<0.05). Reduced cell content of EPA and DHA relative to AA favours the production of aggregatory and proinflammatory eicosanoids that activate leukocytes and platelets. This facilitates inflammation, leukocyte adhesion, platelet aggregation and vaso-occlusion in SCD.     

Lipoprotein-associated phospholipase A2 concentrations in plasma are associated with the extent of coronary artery disease and correlate to adipose tissue levels of marine n-3 fatty acids

Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an emerging risk factor for cardiovascular disease. In the present study, plasma levels of Lp-PLA(2) were measured in patients (n=301) admitted to elective coronary angiography because of suspected coronary artery disease (CAD). In a multiple linear regression analysis, the degree of CAD (0-, 1-, 2- or 3-vessel disease) and plasma LDL cholesterol significantly correlated to Lp-PLA(2) levels. Also the content of the marine n-3 fatty acid, eicosapentaenoic acid (EPA) in adipose tissue, a measure of long-term intake of seafood independently and inversely (r=-0.18, p<0.01) correlated with plasma levels of Lp-PLA(2). The results support the view that Lp-PLA(2) may relate to CAD and that intake of marine n-3 fatty acids might reduce plasma Lp-PLA(2) suggesting another mechanism by which n-3 fatty acids could reduce the risk of cardiovascular disease.     

Plasma polyunsaturated fatty acid profile and delta-5 desaturase activity are altered in patients with type 2 diabetes

Objective

The association between imbalance of polyunsaturated fatty acids (PUFAs), especially low plasma n-3 to n-6 PUFA ratio, and risk of cardiovascular diseases is well known. A balance of plasma PUFAs is determined not only by dietary fatty acid intake, but also by the endogenous fatty acid metabolism, which could be dysregulated by diabetes. In this study, we investigated the plasma n-3 and n-6 PUFA profile and fatty acid desaturase activity in patients with type 2 diabetes (T2D).

Materials/Methods

The subjects were 396 patients with T2D and 122 healthy controls. Plasma eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and dihomo-γ-linolenic acid (DGLA) levels were measured by capillary gas chromatography.

Results

Plasma DHA, AA, and DGLA levels were significantly higher, and EPA levels tended to be lower in patients with T2D than in the controls. Patients with T2D also exhibited significantly lower EPA/AA, DHA/AA, and (EPA + DHA)/AA ratios, and a higher AA/DGLA ratio than the controls. Multiple regression analyses, including age, sex, body mass index, and metabolic parameters in the total population, revealed that the presence of T2D was independently associated with elevated plasma DHA, AA, and DGLA levels and decreased EPA/AA, DHA/AA, and (EPA + DHA)/AA ratios. Furthermore, T2D was independently and positively related to the AA/DGLA ratio, which serves as an estimate of delta (Δ)-5 desaturase activity.

Conclusions

Elevated plasma AA levels and decreased n-3 PUFA/AA ratios in T2D are attributable, at least partly, to Δ5 desaturase activation.