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.     

冠心病患者冠状动脉病变积分与血清游离脂肪酸的相关性分析

目的:探讨冠状动脉病变积分(CAS)与血清游离脂肪酸(FFA)水平的关系.方法:采用ELASA法测定冠心病患者(95例)、非冠心病患者(68例)血清中游离脂肪酸水平.结果:腰围、体质指数、收缩压、舒张压、平均动脉压、脉压指数、高密度脂蛋白胆固醇、FFA均与CAS有显著相关性,多元回归分析显示CAS与FFA和高密度脂蛋白胆固醇存在显著相关性.结论:FFA与CAS有密切相关性,血清FFA可能是冠心病发生发展的良好预测指标.     

Soluble adhesion molecules and marine n-3 fatty acids in patients referred for coronary angiography

OBJECTIVE: To investigate the relationship between soluble cellular adhesion molecules (sCAMs) and the extent of coronary artery disease (CAD) in patients with stable angina pectoris. METHODS AND RESULTS: Two hundred and ninety-one subjects had fasting levels of circulating intercellular adhesion molecule-1(sICAM-1), vascular cellular adhesion molecule-1 (sVCAM-1), sP-selectin and contents of n-3 polyunsaturated fatty acids (n-3 PUFA) in granulocyte membranes and adipose tissue determined before undergoing elective coronary angiography. Levels of soluble VCAM-1 (983+/-216 versus 893+/-196 ng/l, p<0.001), ICAM-1 (318+/-140 versus 290+/-75 ng/l, p<0.05) and P-selectin (90+/-27 versus 80+/-23 ng/l, p<0.01) were significantly increased in subjects with significant CAD compared to subjects with no significant stenoses. In a linear regression analysis, both sVCAM-1 and sP-selectin, but not sICAM-1, correlated to the presence and the severity of CAD. Both sICAM-1 and sP-selectin were significantly correlated to current smoking status and a history of myocardial infarction. The content of total n-3 PUFA and docosahexaenoic acid in adipose tissue was marginally, but significant positively correlated to VCAM-1. CONCLUSION: sVCAM-1 and sP-selectin may serve as markers of CAD in patients with stable angina pectoris. Only sVCAM-1 was weakly correlated to n-3 PUFA in adipose tissue.     

Altered colonic mucosal availability of n-3 and n-6 polyunsaturated fatty acids in ulcerative colitis and the relationship to disease activity

Background and AimsThe polyunsaturated fatty acids (PUFA) arachidonic acid (AA, n-6) and eicosapentaenoic acid (EPA, n-3) are precursors of eicosanoids and other lipid mediators which have critical roles in inflammation. The mediators formed from the different PUFA have different potencies. We hypothesised that metabolic changes associated with colonic mucosal inflammation would modify the bioavailability of the eicosanoid precursors AA and EPA.MethodsColonic mucosa biopsies were obtained from patients with ulcerative colitis and from matched controls. Inflammation was graded endoscopically and histologically. Esterified and non-esterified fatty acids were determined within the biopsies using gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry, respectively.ResultsBiopsy samples were collected from 69 UC patients (54 providing both inflamed and non-inflamed mucosa) and 69 controls. Inflamed mucosa had higher AA (p < 0.001) and lower EPA (p < 0.010) contents and a higher AA:EPA ratio (p < 0.001). Inflamed mucosa also had higher docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) and lower linoleic acid (LA) and α-linolenic acid (α-LNA) contents (all p < 0.001), compared to non-inflamed and controls. There were significant correlations between severity of inflammation and contents of AA, DPA and DHA (positive correlations) and of LA, α-LNA and EPA (negative correlations).ConclusionsHigher AA, AA:EPA ratio, DPA and DHA and lower LA, α-LNA and EPA are seen in inflamed mucosa in UC and correlate with severity of inflammation. This suggests an alteration in fatty acid metabolism in the inflamed gut mucosa, which may offer novel targets for intervention and should be considered if nutritional strategies are used.     

Dietary n-3 fatty acid intake and risk of sudden death and coronary artery disease

Opinion statement Based upon the data from observational epidemiologic studies and randomized clinical trials that are summarized in this article, as well as plausible mechanisms for benefit, the American Heart Association and several international health agencies recommend that all adults eat fish, particularly fatty fish, at least two times per week to lower risk of coronary heart disease (CHD). Patients with established CHD are advised to consume 1 g/d of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) combined. However, many individuals may find it difficult to consume 1 g/d of EPA and DHA, which translates into several meals of fish per week. Thus, fish oil in the form of supplements may be a preferable way to achieve compliance with these recommendations. Because only one large-scale secondary-prevention randomized trial of n-3 fatty acid supplements has been published to date, fish oil supplements have not been routinely recommended after myocardial infarction (MI). However, based upon the present evidence, this treatment option could be considered as one possible avenue to decrease risk of sudden cardiac death (SCD) in the early post-MI period when implantable cardioverter-defibrillator (ICD) therapy appears to be less efficacious. n-3 Fatty acid supplements are currently not indicated for prevention of recurrent ventricular arrhythmias in patients with ICDs due to the conflicting and primarily null randomized trial results in this patient population. Finally, based upon the current state of evidence, it is unclear whether dietary intake of α-linolenic acid (ALA), a plant-based intermediate-chain n-3 fatty acid, influences risk of CHD or SCD. Therefore, increasing intake of ALA specifically for the prevention of CHD cannot be recommended at this time.     

Effects of dietary supplementation with n-3 fatty acids compared with n-6 fatty acids on bronchial asthma

OBJECTIVE: The effects of perilla seed oil (n-3 fatty acids) on bronchial asthma were compared with the effects of corn oil (n-6 fatty acids) in relation to the pulmonary function and the generation of leukotriene B4 (LTB4) and C4 (LTC4) by leucocytes. METHODS AND SUBJECTS: 14 asthmatic subjects were divided randomly into two groups: one group (7 subjects) consumed perilla seed oil-rich supplementation and the other group (7 subjects) consumed corn oil-rich supplementation for 4 weeks. Generation of LTs by leucocytes and respiratory function were compared between the two groups. RESULTS: The generation of LTB4 and LTC4 by leucocytes tended to increase in subjects (N=7) with corn oil-rich supplementation, and decrease in subjects (N=7) with perilla seed oil-rich supplementation. Significant differences between the two groups were observed in the generation of LTB4 at 2 weeks (p<0.05) and LTC4 at 2 weeks (p<0.05) after dietary supplementation. Significant increases in the value of PEF (p<0.05), FVC (p<0.01), FEV(1.0) (p<0.05) and V(25) (p<0.05) were found in subjects who received perilla seed oil supplementation for 4 weeks. And significant differences in the value of FVC (p<0.05) and FEV(1.0) (p<0.05) were observed between the two groups after 4 weeks of dietary supplementation. CONCLUSION: These results suggest that perilla seed oil-rich supplementation is useful for the treatment of asthma in terms of suppression of LTB4 and LTC4 generation by leucocytes, and improvement of pulmonary function.     

Altered hemoglobin-oxygen affinity with long-term propranolol therapy in patients with coronary artery disease

Pharmacologic agents that alter hemoglobin affinity for oxygen may affect systemic or myocardial oxygen delivery. In vitro, and in normal man, propranolol shifts the oxyhemoglobin equilibrium curve to the right, thus increasing the partial pressure of oxygen at which hemoglobin is 50 percent saturated (P₅₀) and enhancing oxygen delivery. The effect of propranolol on hemoglobin P₅₀ was evaluated in 12 patients with angina pectoris and documented coronary artery disease. Determinations were made during oral propranolol therapy (mean daily dose 152 mg) of at least 3 months' duration and after administration of propranolol had been discontinued for at least 4 days. Hemoglobin P₅₀ and erythrocyte 2,3-diphosphoglycerate (DPG) were measured. Data in 12 patients were: the mean P₅₀ after discontinuation of propranolol was 28.2 mm Hg ± 0.9 (standard error of the mean) and during propranolol therapy 31.7 ± 0.7; P < 0.001; red blood cell 2, 3-DPG did not change to explain the increase in P₅₀. This demonstrated shift could increase systemic oxygen delivery and thus benefit marginally perfused myocardium while sparing coronary flow. Propranolol, in addition to its negative chronotropic and inotropic effects, may increase tissue oxygen delivery in patients with the anginal syndrome.     

Relation of omega-3 fatty acid and C-reactive protein to peripheral artery disease in patients with coronary artery disease

Eicosapentaenoic acid (EPA), a member of the omega-3 polyunsaturated fatty acid family, prevents cardiovascular disease. C-reactive protein (CRP) is a marker of inflammation, which promotes atherosclerosis. The aim of this study was to investigate the relationship among EPA, CRP, and the prevalence of peripheral artery disease (PAD), which is a manifestation of systemic atherosclerosis. A cross-sectional study was performed on 238 patients with coronary artery disease (CAD). Blood EPA and CRP levels and ankle-brachial pressure indices were measured. Cut-off values for plasma EPA levels and serum CRP levels were determined using receiver operating characteristic (ROC) analysis. Patients with ABIs ≤0.9 were defined as having PAD. EPA levels were significantly lower and CRP levels were significantly higher in patients with PAD than in those without [48 (26–77) vs. 58 (41–83) μg/ml, p = 0.026 and 3.3 (0.64–14.0) vs. 0.70 (0.32, 2.4) mg/l, p = 0.004]. Multivariate analysis for PAD revealed that high CRP levels and low EPA levels were significant and independent predictors of PAD [odds ratio 3.1 (95 % CI 1.4–6.9), p = 0.006 and odds ratio 4.9 (95 % CI 1.5–9.7), p = 0.004]. Furthermore, to predict PAD, adding high CRP levels and low EPA levels to the established risk factors significantly improved the area under the ROC curves, from 0.66 to 0.78, of the PAD prediction model (p = 0.004). A significant relationship among EPA, CRP, and PAD was confirmed in patients with CAD.     

Heart rate variability and n-3 polyunsaturated fatty acids in patients with diabetes mellitus

Abstract. Hagstrup Christensen J, Aarup Skou H, Madsen T, Tørring I, Berg Schmidt E (Aalborg Hospital, Aalborg; and Hjørring/Brønderslev Hospital, Hjørring, Denmark). Heart rate variability and n‐3 polyunsaturated fatty acids in patients with diabetes mellitus. J Intern Med 2001; 249: 545–552. Objectives. Dietary n‐3 polyunsaturated fatty acids (PUFA) derived from fish may reduce the incidence of sudden cardiac death (SCD). The aim of the present study was to examine associations between n‐3 PUFA and 24‐h heart rate variability in patients with type 1 and type 2 diabetes mellitus (DM). Design. Observational study. Setting. The out‐patient’s diabetic clinic at Hjørring Hospital, Hjørring, Denmark. Subjects. Forty‐three patients with type 1 DM and 38 patients with type 2 DM. Main outcome measures. The patients fulfilled a food‐questionnaire regarding fish consumption, whilst the content of n‐3 PUFA in platelets was measured and 24‐h heart rate variability (HRV) was obtained. Results. The patients fish consumption was strongly related to their content of n‐3 PUFA in platelets. Furthermore, in patients with type 1 DM a close positive association was found between the content of n‐3 PUFA in platelets and 24‐h HRV. This association was not significant in patients with type 2 DM. Conclusions. The positive association between n‐3 PUFA in platelets and HRV may indicate a beneficial effect of n‐3 PUFA on HRV in patients with type 1 DM. Further studies are warranted to clarify whether supplementation with n‐3 PUFA reduce the risk of SCD amongst patients with DM.     

冠心病患者伴非酒精性脂肪性肝病的临床特征分析

目的 分析冠心病(CAD)伴非酒精性脂肪性肝病(NAFLD)患者的临床特征.方法 234例接受冠状动脉造影检查的患者,并有糖、脂代谢指标及腹部超声检查结果,男性148例,女性86例,平均年龄66.6岁.应用冠脉狭窄指数(CSI)评价冠状动脉病变严重程度,代谢综合征采用2007年中国成人血脂异常防治指南中关于代谢综合征的诊断标准.结果 234例研究对象中,62例患者为NAFLD.与无NAFLD组相比,NAFLD患者中心性肥胖的患病率明显升高(75.8%对50.0%,P<0.01).CAD伴NAFLD在60岁以下患者中的发生率显著高于60岁以上者(27.4%对13.7%,P=0.005).尽管CAD亚组与CAD合并NAFLD亚组的CSI评分差异无统计学意义(P>0.05),但后者的年龄明显低于CAD亚组(P=0.006).Logistic回归分析显示中心性肥胖为NAFLD的独立危险因子(β:1.701,P<0.001).Logistic回归与多元逐步回归分析发现,年龄分别是影响冠脉病变的独立危险因素(β=0.032,P=0.027)以及影响CSI评分的主要因素(β=0.125,P=0.022).结论 中年肥胖及脂肪肝人群应当重视冠心病的筛查.     

Effects of n-3 fatty acids in essential hypertension

We examined the effects on blood pressure, plasma lipoproteins, and platelet function when marine oil supplements (rich in n-3 fatty acids) or vegetable oil supplements (rich in n-6 fatty acids) were added to the usual diets of patients with mild essential hypertension. In a randomized, double-blind, parallel-group study, patients received 50 g of either marine oil (n = 8) or vegetable oil (n = 8) daily for 6 weeks following a baseline observation period. Diastolic blood pressure declined during treatment with fish oil (mean +/- SEM, 96 +/- 2 v 89 +/- 2 mm Hg, P = .02), but did not change with vegetable oil (92 +/- 1 v 94 +/- 1 mm Hg). Systolic blood pressure did not change significantly during either treatment. Serum triglycerides declined (by approximately 30%) in patients receiving only marine oil, but total cholesterol, LDL-, HDL-, HDL2-, and HDL3-cholesterol-subfractions and apolipoproteins A-I and B were unchanged in both treatment groups. Bleeding time increased by 33% during treatment with marine oil but did not change with vegetable oil supplements. Marine oil did not alter in vitro platelet aggregation thresholds. The lack of a significant correlation between blood pressure changes and platelet membrane fluidity, plasma renin activity, aldosterone, norepinephrine, or epinephrine suggests that these variables did not mediate the antihypertensive effect of the marine oil. We conclude that large doses of marine oil reduce diastolic blood pressure, lower triglycerides, and increase bleeding time in patients with mild hypertension.     

n-3多聚不饱和脂肪酸与心血管疾病

在发达国家,心血管疾病为其主要死亡原因,在发展中国家,心血管疾病的发病率逐年增加。根据2000年中国卫生年鉴公布的资料显示,心血管（包括脑血管）病的死亡率无论在城市还是农村均居于首位。如何预防心血管疾病,控制其病情,改善其预后为当代医学的主要研究课题之一。在西方国家的研究中,鱼油被认为具有心血管保护作用。