Alexithymia and depression in the recovery of chronic pain patients: a follow-up study.

BACKGROUND: Childhood adversities and emotional dysregulation are connected with chronic pain, alexithymia, and depression. Longitudinal studies exploring the impact of their co-occurrence on the pain situation are rare. AIMS: The influence of alexithymia, depression, baseline pain situation, and treatment options on the course of chronic pain in a clinical sample was studied. METHODS: The baseline data was collected from chronic pain patients (n = 154) before their first pain clinic visit, and the follow-up data after 1 year by self-report questionnaires. Study variables consisted of pain intensity, pain disability, alexithymia (TAS-20), depression (BDI-II), and treatment interventions. Statistical analyses were performed to find out differences between baseline and follow-up, as well as between alexithymic and non-alexithymic patients, and to estimate the effect of the treatment provided. RESULTS: At follow-up, the majority of the patients had pain intensity and disability severe enough to disrupt with their daily living. None of treatment interventions was related to better outcome. Alexithymic patients reported more pain disability and depression at both baseline and at follow-up. The effect of alexithymia on pain disability was mediated by depression. The use of opioids was connected to alexithymia and depressiveness. Alexithymia and depression made a substantial contribution to poorer outcome. CONCLUSIONS: Severe pain intensity and disability with depression and alexithymia predicted difficulties in achieving improvement. Depression and alexithymia probably impair compliance with treatment and adherence to interventions. Their co-occurrence with a more severe pain situation and with the use of opioids indicates psychological problems underlying the pain experience.

Longitudinal associations of serum fatty acid composition with type 2 diabetes risk and markers of insulin secretion and sensitivity in the Finnish Diabetes Prevention Study.

PURPOSE: To examine the longitudinal associations of serum fatty acid composition with type 2 diabetes, insulin secretion and insulin sensitivity over several years. METHODS: We conducted a prospective cohort study derived from the randomized Finnish Diabetes Prevention Study. Total serum fatty acid composition was measured using gas chromatography in 407 overweight, middle-aged people with impaired glucose tolerance at baseline (1993-1998) and annually during the intervention period (1994-2000). Longitudinal associations of 20 fatty acids and three desaturase activities (Δ5 (20:4n-6/20:3n-6, D5D), Δ6 (18:3n-6/18:2n-6, D6D), stearoyl-CoA desaturase-1 (16:1n-7/16:0, SCD-1)) with type 2 diabetes incidence, and estimates of insulin sensitivity (Matsuda), secretion (ratio of insulin and glucose concentrations) and ß-cell function (disposition index) by an oral glucose tolerance test were analyzed using Cox regression and linear mixed models. We validated estimated D5D and D6D using a known FADS1 gene variant, rs174550. RESULTS: The baseline proportions of 20:5n-3, 22:5n-3 and 22:6n-3, and D5D were associated with lower incidence of type 2 diabetes during a median follow-up of 11 years (HR per 1SD: 0.72, 0.74, 0.73, 0.78, respectively, P ≤ 0.01). These long-chain omega-3 fatty acids and D5D were associated with higher insulin sensitivity in subsequent years but not with disposition index. Saturated, monounsaturated and trans fatty acids and 18:3n-3, 18:2n-6, SCD-1 and D6D were inconsistently associated with type 2 diabetes or related traits. CONCLUSIONS: Serum long-chain omega-3 fatty acids and D5D predicted lower type 2 diabetes incidence in people at a high risk of diabetes attending to an intervention study; a putative mechanism behind these associations was higher insulin sensitivity.

The role of alexithymia: An 8-year follow-up study of chronic pain patients.

OBJECTIVE: The aim of this 8-year follow-up study was to ascertain changes in alexithymia, depressiveness and pain situation in a sample of chronic pain patients and to explore the impact of alexithymia and depression on the outcome. METHODS: Participants (n=83) were chronic non-malignant pain patients who completed self-report study questionnaires before their first visit to the pain clinic and again 8years later. Study variables consisted of pain intensity measured by the Visual Analogous Scale, the Pain Disability Scale, the Toronto Alexithymia Scale and the Beck Depression Inventory. The moderate improvement in the pain situation was estimated as a decrease of 30% or more in pain intensity or pain disability. RESULTS: In the whole sample there was a significant decrease in pain intensity, pain disability and depressiveness, but only some of the patients achieved moderate improvement in their pain situation. Alexithymia remained stable during the 8-year period. The alexithymic patients had poorer pain situation and more depressiveness both at baseline and at follow-up. Unfavorable outcome in the pain situation was connected with male gender and alexithymia at baseline but not with depressiveness. Alexithymia and depressiveness were closely related to each other and the connection strengthened during the follow-up period. CONCLUSION: Alexithymic depressive chronic pain patients represent a special, more disabled subgroup among chronic pain patients. The authors recommend screening for and identifying alexithymia and depression in chronic pain patients. Structural treatment protocols such as cognitive-behavioral therapy may benefit these patients. More research is needed to develop treatment interventions for alexithymic patients.

Alexithymia and Early Maladaptive Schemas in chronic pain patients.

Psychological factors have an impact on subjective pain experience. The aim of this study was to explore the occurrence of alexithymia and Early Maladaptive Schemas in a sample of 271 first visit chronic pain patients of six pain clinics. The patients completed the study questionnaire consisting of the Toronto Alexithymia Scale-20, the Finnish version of the Young Schema Questionnaire short form-extended, the Beck Depression Inventory-II, and pain variables. Alexithymic patients scored higher on Early Maladaptive Schemas and had more pain intensity, pain disability and depression than nonalexithymic patients. Both alexithymia and depression correlated significantly with most Early Maladaptive Schemas. The co-occurrence of alexithymia, Early Maladaptive Schemas and depression seems to worsen the pain experience. Screening of alexithymia, depression and Early Maladaptive Schemas may help to plan psychological treatment interventions for chronic pain patients.

Short- and long-term outcome following laparoscopic versus open resection for carcinoma of the rectum in the multimodal setting.

BACKGROUND: Laparoscopic resection for rectal cancer has remained controversial because of the lack of level 1 evidence regarding oncologic safety and long-term survival. OBJECTIVES: The aim of this study was to assess the impact of laparoscopic versus open resection for rectal cancer on clinical and oncologic outcome in the multimodal setting. DESIGN: This is a review of prospectively gathered data from a single-institution rectal cancer database. SETTINGS: This study was conducted in the Central Hospital of Central Finland. PATIENTS: From January 1999 to December 2006, 191 selected patients were included. INTERVENTIONS: One hundred patients underwent laparoscopic resection, and 91 patients, also suitable for laparoscopic surgery, underwent open major rectal resection in the multimodal setting. MAIN OUTCOME MEASURES: The main measures of outcome were early recovery and short- and long-term morbidity; local recurrence and survival were secondary outcomes. LIMITATIONS: This is not a randomized study. RESULTS: The study groups were balanced for baseline characteristics. Conversion rate to open surgery was 22%. Laparoscopic surgery resulted in significantly less bleeding (175 mL vs 500 mL, p < 0.001), 1 day earlier recovery of normal diet (3 days vs 4 days, p = 0.001), and shorter postoperative hospital stay (7 days vs 9 days, p < 0.001). Postoperative 30-day mortality (1% vs 3%), morbidity (31% vs 43%), readmission (11% vs 15%), and reoperation (6% vs 9%) rates were similar in the 2 groups, but significantly fewer patients in the laparoscopic group had long-term complications (19% vs 36%, p = 0.033). The 5-year disease-free survival (78% vs 80%, p = 0.74) and local recurrence (5% vs 6%, p = 0.66) rates were similar in the laparoscopic and open group for those 175 patients treated for cure. CONCLUSION: Laparoscopic surgery resulted in faster postoperative recovery and fewer long-term complications than open surgery without apparently compromising the long-term oncologic outcome. Our results indicate that laparoscopic rectal resection is an acceptable alternative to open surgery in selected patients with rectal cancer.

Early maladaptive schemas in Finnish adult chronic pain patients and a control sample.

Engel (1959) suggested that negative physical or emotional experiences in childhood predispose to the development of chronic pain. Studies have shown that physical and sexual abuse in early life is connected with chronic pain. Emotional adversities are much less studied causes contributing to the development of chronic pain and disability. Early emotional abuse, neglect, maltreatment and other adversities are deleterious childhood experiences which, according to Young's schema theory (1990), produce early maladaptive schemas (EMSs). The primary goal of this study was to examine whether early adversities were more common in chronic pain patients than in a control group. A total of 271 (53% women) first-visit chronic pain patients and 331 (86% women) control participants took part in the study. Their socio-demographic data, pain variables and pain disability were measured. To estimate EMSs the Young Schema Questionnaire was used. Chronic pain patients scored higher EMSs reflecting incapacity to perform independently, catastrophic beliefs and pessimism. The most severely disabled chronic pain patients showed an increase in all the EMSs in the Disconnection and Rejection schema domain, namely Abandonment/Instability, Mistrust/Abuse, Emotional Deprivation, Defectiveness/Shame and Social Isolation/Alienation EMSs. The results of the study suggested that chronic pain patients had suffered early emotional maltreatment.

A psyllium fiber-enriched meal strongly attenuates postprandial gastrointestinal peptide release in healthy young adults.

Dietary fiber (DF) and protein are essential constituents of a healthy diet and are well known for their high satiety impact. However, little is known about their influence on postprandial gastrointestinal (GI) peptide release. Our aim in this single-blind, randomized, cross-over study was to investigate the effects of DF and/or protein enrichments on satiety-related metabolic and hormonal responses. Sixteen healthy, nonobese volunteers participated in the study and ingested 1 of 5 isoenergetic test meals in a randomized order on separate days. The test meals were as follows: 1) low in protein (2.8 g) and fiber (7.6 g); 2) low in protein (2.6 g) and high in soluble fiber (psyllium, 23.0 g); 3) high in protein (soy, 19.7 g) and low in fiber (6.2 g); 4) high in protein (18.4 g) and fiber (23.0 g); and 5) white wheat bread. Serum insulin and plasma glucose, ghrelin, glucagon-like peptide 1 (GLP-1), and peptide YY (PYY) concentrations were determined for 2 h following the meals. In addition, hunger and satiety ratings were collected. Postprandial glucose, insulin, ghrelin, GLP-1, and PYY responses all differed among the meals (P

Interlamellar coupling of phospholipid bilayers in liposomes: an emergent property of lipid rearrangement.

The thermal phase behaviors of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) large unilamellar vesicles (LUVs) and multilamellar vesicles (MLVs) were compared by fluorescence spectroscopy, using PPDPC (1-palmitoyl-2[10-(pyren-1-yl)]decanoyl-sn-glycero-3-phosphocholine) as a reporter, in parallel with differential scanning calorimetry (DSC). A striking difference is seen between MLVs and LUVs in the lateral organizational dynamics of PPDPC, in particular, below the main phase transition temperature T(m), with efficient clustering of PPDPC into fluid microdomains in the L(beta') and P(beta') (ripple) phases of DPPC MLVs. In the P(beta') phase of MLVs, the probe is likely to become enriched in linear line defects, restricting intermolecular collisions to occur in a quasi one-dimensional system. In contrast, fluorescence and DSC data both suggest that the P(beta') phase is not well-defined in LUVs. Fluorescence anisotropy for 1-palmitoyl-2-[3-(diphenylhexatrienyl)propanoyl]-sn-glycero-3-phosphocholine (DPH-PC) revealed similar acyl chain order for both LUVs and MLVs in the L(beta') and P(beta') phases. However, for MLVs with this probe, T(m) determined from anisotropy was elevated by 0.7 degrees, with higher anisotropy evident in the L(alpha) phase compared to LUVs. These differences in the thermal phase behavior of the two types of liposomes are likely to derive from the augmented acyl chain order due to cooperative coupling of the lamellae of DPPC MLVs, thus manifesting in new, emerging material properties in the latter type of bilayer membrane assembly, as reflected in the organizational dynamics of the pyrene-labeled analogue.

Viscosity of oat bran-enriched beverages influences gastrointestinal hormonal responses in healthy humans.

Viscous fibers, including beta-glucan in oat bran, favorably affect satiety as well as postprandial carbohydrate and lipid metabolism. However, effects of fiber viscosity on modulation of satiety-related gut hormone responses are largely unknown. We examined the effects of modified oat bran, with or without its natural viscosity, on sensations of appetite and satiety-related gastrointestinal (GI) hormone responses to establish the relevance of viscosity of beta-glucan in oat bran. Twenty healthy, normal-weight participants (16 female, 4 male, aged 22.6 +/- 0.7 y) ingested 2 isocaloric (1250 kJ) 300-mL oat bran beverages with low or high viscosity (carbohydrates, 57.9 g; protein, 7.8 g; fat, 3.3 g; fiber, 10.2 g) after a 12-h fast in randomized order. Viscosity of the low-viscosity oat bran beverage was reduced by beta-glucanase treatment. Blood samples were drawn before and 15, 30, 45, 60, 90, 120, and 180 min after beverage consumption. The oat bran beverage with low viscosity induced a greater postprandial increase in satiety (P = 0.048) and plasma glucose (P < 0.001), insulin (P = 0.008), cholecystokinin (P = 0.035), glucagon-like peptide 1 (P = 0.037), and peptide YY (P = 0.051) and a greater decrease in postprandial ghrelin (P = 0.009) than the beverage with high-viscosity oat bran. Gastric emptying as measured by paracetamol absorption was also faster (P = 0.034) after low-viscosity oat bran beverage consumption. In conclusion, viscosity differences in oat beta-glucan in a liquid meal with identical chemical composition strongly influenced not only glucose and insulin responses, but also short-term gut hormone responses, implying the importance of food structure in the modulation of postprandial satiety-related physiology.

High-affinity small molecule-phospholipid complex formation: binding of siramesine to phosphatidic acid.

Siramesine (SRM) is a sigma-2 receptor agonist which has been recently shown to inhibit growth of cancer cells. Fluorescence spectroscopy experiments revealed two distinct binding sites for this drug in phospholipid membranes. More specifically, acidic phospholipids retain siramesine on the bilayer surface due to a high-affinity interaction, reaching saturation at an apparent 1:1 drug-acidic phospholipid stoichiometry, where after the drug penetrates into the hydrocarbon core of the membrane. This behavior was confirmed using Langmuir films. Of the anionic phospholipids, the highest affinity, comparable to the affinities for the binding of small molecule ligands to proteins, was measured for phosphatidic acid (PA, mole fraction of X(PA) = 0.2 in phosphatidylcholine vesicles), yielding a molecular partition coefficient of 240 +/- 80 x 10(6). An MD simulation on the siramesine:PA interaction was in agreement with the above data. Taking into account the key role of PA as a signaling molecule promoting cell growth our results suggest a new paradigm for the development of anticancer drugs, viz. design of small molecules specifically scavenging phospholipids involved in the signaling cascades controlling cell behavior.

Effects of fatty and lean fish intake on blood pressure in subjects with coronary heart disease using multiple medications.

BACKGROUND: Intake of fish and long-chain n-3 fatty acids has been of wide interest due to their beneficial effects on cardiovascular risk factors and lower coronary heart disease (CHD) risk. AIM OF THE STUDY: The aim of this pilot study was to examine the effects of fatty fish and lean (white) fish on fatty acid composition of serum lipids and cardiovascular risk factors in subjects with CHD using multiple drugs for this condition. METHODS: The study was an 8-week controlled, parallel intervention. Inclusion criteria were myocardial infarction or unstable ischemic attack, age under 70 years, use of betablockers and presence of sinus rhythm. The subjects were randomized to one of the following groups: 4 meals/week fatty fish (n = 11), 4 meals/week lean fish (n = 12) and control diet including lean meat (n = 10). RESULTS: The mean (+/-SD) of reported fish meals per week was 4.3 +/- 0.4, 4.7 +/- 1.1 and 0.6 +/- 0.4 in the groups, respectively. The proportions of eicosapentaenoic and docosahexaenoic acids in serum lipids increased in the fatty fish group only (P < 0.05). Systolic and diastolic blood pressure levels decreased in the lean fish group (0 vs. 8 week: 3.5 +/- 3.2 and 4.6 +/- 3.6%, respectively, P < 0.05). Serum total triglyceride concentration did not significantly change. HDL cholesterol concentration change differed among groups but without significant post hoc differences. Apolipoprotein A-1 concentration decreased in the control group (0 vs. 8 week, P < 0.05). Coagulation factors, 25-hydroxy vitamin D, and heart rate variability (24 h Holter) did not change among the groups. CONCLUSIONS: Our results suggest that intake of lean fish at least four times per week could reduce blood pressure levels in CHD patients.

The G-250A polymorphism in the hepatic lipase gene promoter is associated with changes in hepatic lipase activity and LDL cholesterol: The KANWU Study.

BACKGROUND AND AIMS: Hepatic lipase (HL) catalyzes the hydrolysis of triglycerides and phospholipids from lipoproteins, and promotes the hepatic uptake of lipoproteins. A common G-250A polymorphism in the promoter of the hepatic lipase gene (LIPC) has been described. The aim was to study the effects of the G-250A polymorphism on HL activity, serum lipid profile and insulin sensitivity. METHODS AND RESULTS: Altogether 151 healthy subjects (age 49+/-8 years, BMI 26.5+/-3.0kg/m(2)) were randomly assigned for 3 months to an isoenergetic diet containing either a high proportion of saturated fatty acids (SFA diet) or monounsaturated fatty acids (MUFA diet). Within groups there was a second random assignment to supplements with fish oil (3.6g n-3 FA/day) or placebo. At baseline, the A-250A genotype was associated with high serum LDL cholesterol concentration (P=0.030 among three genotypes). On the MUFA diet carriers of the A-250A genotype presented a greater decrease in LDL cholesterol concentration than subjects with other genotypes (P=0.007 among three genotypes). The rare -250A allele was related to low HL activity (P<0.001 among three genotypes). The diet did not affect the levels of HL activity among the genotypes. CONCLUSION: The A-250A genotype of the LIPC gene was associated with high LDL cholesterol concentration, but the MUFA-enriched diet reduced serum LDL cholesterol concentration especially in subjects with the A-250A genotype.

Association between ghrelin gene variations and blood pressure in subjects with impaired glucose tolerance.

BACKGROUND: Ghrelin is a gut-brain hormone, which stimulates food intake and controls energy balance. Recently, it has been shown that ghrelin may also play a role in the regulation of blood pressure (BP) by acting at the sympathetic nervous system. In the present study we genotyped six variants of the ghrelin gene and its promoter, and tested whether these single nucleotide polymorphisms (SNPs) were associated with BP levels in participants of the Finnish Diabetes Prevention Study. METHODS: The Finnish Diabetes Prevention Study was a longitudinal study where 522 subjects with impaired glucose tolerance were randomized into either an intervention or control group. DNA was available from 507 subjects (mean body mass index [BMI] 31.2+/-4.5 kg/m2, age 55+/-7 years). All six SNPs were screened by the restriction fragment length polymorphism method. RESULTS: Subjects with the most common genotype combination of the following four SNPs, -604G/A, -501A/C, Leu72Met, and Gln90Leu, had the lowest systolic (131+/-11 v 137+/-13 mm Hg, P=.003) and diastolic BP levels (79+/-7 v 83+/-7 mm Hg, P=.004) at the baseline of the study and during 3 years of follow-up compared to all other genotypes. Adjustments for age, gender, antihypertensive medication, BMI, waist circumference, and alcohol intake did not change this association. CONCLUSIONS: Several ghrelin gene variations were associated with BP levels in subjects with impaired glucose tolerance.

Evolutionary divergence of the necroptosis effector MLKL.

The pseudokinase, MLKL (mixed-lineage kinase domain-like), is the most terminal obligatory component of the necroptosis cell death pathway known. Phosphorylation of the MLKL pseudokinase domain by the protein kinase, receptor interacting protein kinase-3 (RIPK3), is known to be the key step in MLKL activation. This phosphorylation event is believed to trigger a molecular switch, leading to exposure of the N-terminal four-helix bundle (4HB) domain of MLKL, its oligomerization, membrane translocation and ultimately cell death. To examine how well this process is evolutionarily conserved, we analysed the function of MLKL orthologues. Surprisingly, and unlike their mouse, horse and frog counterparts, human, chicken and stickleback 4HB domains were unable to induce cell death when expressed in murine fibroblasts. Forced dimerization of the human MLKL 4HB domain overcame this defect and triggered cell death in human and mouse cell lines. Furthermore, recombinant proteins from mouse, frog, human and chicken MLKL, all of which contained a 4HB domain, permeabilized liposomes, and were most effective on those designed to mimic plasma membrane composition. These studies demonstrate that the membrane-permeabilization function of the 4HB domain is evolutionarily conserved, but reveal that execution of necroptotic death by it relies on additional factors that are poorly conserved even among closely related species.

Gene-diet interaction of a common FADS1 variant with marine polyunsaturated fatty acids for fatty acid composition in plasma and erythrocytes among men.

SCOPE: Limited information exists on how the relationship between dietary intake of fat and fatty acids in erythrocytes and plasma is modulated by polymorphisms in the FADS gene cluster. We examined gene-diet interaction of total marine PUFA intake with a known gene encoding Δ-5 desaturase enzyme (FADS1) variant (rs174550) for fatty acids in erythrocyte membranes and plasma phospholipids (PL), cholesteryl esters (CE), and triglycerides (TG). METHODS AND RESULTS: In this cross-sectional study, fatty acid compositions were measured using GC, and total intake of polyunsaturated fat from fish and fish oil was estimated using a food frequency questionnaire in a subsample (n = 962) of the Metabolic Syndrome in Men Study. We found nominally significant gene-diet interactions for eicosapentaenoic acid (EPA, 20:5n-3) in erythrocytes (pinteraction = 0.032) and for EPA in plasma PL (pinteraction = 0.062), CE (pinteraction = 0.035), and TG (pinteraction = 0.035), as well as for docosapentaenoic acid (22:5n-3) in PL (pinteraction = 0.007). After excluding omega-3 supplement users, we found a significant gene-diet interaction for EPA in erythrocytes (pinteraction < 0.003). In a separate cohort of the Kuopio Obesity Surgery Study, the same locus was strongly associated with hepatic mRNA expression of FADS1 (p = 1.5 × 10(-10) ). CONCLUSION: FADS1 variants may modulate the relationship between marine fatty acid intake and circulating levels of long-chain omega-3 fatty acids.

Association of the Pro12Ala polymorphism in the PPAR-gamma2 gene with 3-year incidence of type 2 diabetes and body weight change in the Finnish Diabetes Prevention Study.

The association of the Pro12Ala polymorphism of the PPAR-gamma2 gene with the incidence of type 2 diabetes was investigated in 522 subjects with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study. Subjects were randomized to either an intensive diet and exercise group or a control group. By 3 years of intervention, the odds ratio of the development of type 2 diabetes for subjects with the Ala12 allele was 2.11-fold compared with that for subjects with the Pro12Pro genotype (95% CI 1.20-3.72). The risk for type 2 diabetes increased also in subjects who gained weight or belonged to the control group. In the intervention group, subjects with the Ala12Ala genotype lost more weight during the follow-up than subjects with other genotypes (Pro12Pro vs. Ala12Ala P = 0.043), and none of subjects with the Ala12Ala genotype developed type 2 diabetes in this group. In conclusion, the Ala12 allele may predispose to the development of type 2 diabetes in obese subjects with IGT. However, beneficial changes in diet, increases in physical activity, and weight loss may reverse, to some extent, the diabetogenic impact of the Ala12 allele, possibly due to an improved insulin sensitivity.

Antibodies against oxidized LDL and cardiolipin and mortality in patients with coronary heart disease.

The association between antibodies against oxidized LDL (oxLDL) and cardiolipin and the risks of death and cardiovascular disease events were evaluated in patients with established coronary heart disease (CHD). The patients (mean age: 61 years, range: 33-74 years) were participants in the EUROASPIRE study; 108 of them had undergone coronary artery bypass surgery, 106 had balloon angioplasty, 101 had a diagnosis of acute myocardial infarction (AMI), and 98 acute myocardial ischemia. Antibodies against oxLDL and cardiolipin were measured and incidence of CHD events and deaths were followed up for 5 years in 284 men and 129 women. During the follow-up 36 patients died and 21 had AMI. After adjustment for cardiovascular disease risk factors the relative risks (RR [95% confidence interval]) of death were 1 (reference), 2.50 (0.97-6.49) and 2.21 (0.85-5.80) in increasing tertile categories of anti-oxLDL antibody titers, respectively (P for trend 0.16). The risks of CHD-death or AMI combined were 1 (reference), 2.61 (1.02-6.65) and 1.06 (0.37-3.03) in increasing tertile categories of anticardiolipin antibody titers, respectively (P for trend 0.03). In conclusion, the results suggest that antibodies against oxLDL and cardiolipin are not major predictors of risks of death and CHD events in patients with established CHD.

n-3 Fatty acids and 5-y risks of death and cardiovascular disease events in patients with coronary artery disease.

BACKGROUND: Data on the association of n-3 fatty acid content in serum lipids with mortality in patients with coronary artery disease (CAD) are limited. OBJECTIVE: We hypothesized that a high proportion of n-3 fatty acids in serum lipids would be associated with reduced risks of death and coronary events in patients with established CAD. DESIGN: We measured dietary intakes via food records and the fatty acid composition of serum cholesteryl esters (CEs) in 285 men and 130 women with CAD (x age: 61 y; range: 33-74 y). The patients participating in the EUROASPIRE (European Action on Secondary Prevention through Intervention to Reduce Events) study were followed up for 5 y. RESULTS: During the follow-up, 36 patients died, 21 had myocardial infarctions, and 12 had strokes. The relative risks (RRs) of death adjusted for cardiovascular disease risk factors for subjects in the highest tertile of fatty acids in CEs compared with those in the lowest tertile were 0.33 (95% CI: 0.11, 0.96) for alpha-linolenic acid, 0.33 (0.12, 0.93) for eicosapentaenoic acid, and 0.31 (0.11, 0.87) for docosahexaenoic acid (P for trend = 0.063, 0.056, and 0.026, respectively). A high proportion of eicosapentaenoic acid in CEs was associated with a low risk of CAD death. Compared with no consumption, consumption of fish tended to be associated with a lower risk of death [1-57 g/d, RR = 0.50 (0.20, 1.28); > 57 g/d, RR = 0.37 (0.14, 1.00); P for trend = 0.059]. CONCLUSION: High proportions of n-3 fatty acids in serum lipids are associated with a substantially reduced risk of death.

Association of the fatty acid profile of serum lipids with glucose and insulin metabolism during 2 fat-modified diets in subjects with impaired glucose tolerance.

BACKGROUND: Both the amount and quality of dietary fat can modify glucose and insulin metabolism. OBJECTIVE: The objective was to examine the relation between serum lipid fatty acids and glucose metabolism before and after the consumption of a diet enriched in either monounsaturated (Mono diet) or polyunsaturated (Poly diet) fatty acids. DESIGN: After consuming a high-saturated-fat run-in diet for 3 wk, 31 subjects with impaired glucose tolerance were randomly counseled to consume the Mono [40% fat; 11%, 19%, and 8% of energy as saturated, monounsaturated, and polyunsaturated fatty acids (S:M:P), respectively] or the Poly (34% fat; S:M:P of 11%:10%:10%) diet for 8 wk. Serum lipid fatty acids were measured, and an intravenous-glucose-tolerance test was performed at baseline and at 8 wk. RESULTS: At baseline, a higher glucose effectiveness (S(G)) was associated with higher proportions of oleic (r = 0.57, P = 0.04) and alpha-linolenic (r = 0.64, P = 0.01) acids in phospholipids. An increase in the proportions of oleic and alpha-linolenic acids in phospholipids was associated with a decrease in fasting plasma glucose [r = -0.53 (P = 0.002) and r = -0.47 (P = 0.009), respectively]. An increase in the S(G) was associated with an increase in the proportion of oleic acid (r = 0.55, P = 0.004) and with a decrease in that of arachidonic acid (r = -0.40, P = 0.04) in phospholipids. CONCLUSIONS: The beneficial changes in fasting plasma glucose and in the S(G) during the Mono diet were associated with alterations in the proportions of oleic, alpha-linolenic, and arachidonic acids in phospholipids.

Leucine7 to proline7 polymorphism in prepro-NPY gene and femoral neck bone mineral density in postmenopausal women.

Neuropeptide Y (NPY) is a versatile neurotransmitter that has recently been shown to regulate bone metabolism in animal and in vitro studies. We studied the influence of leucine7-to-proline7 (Leu7/Pro7) polymorphism of the NPY signal peptide gene on bone mineral density (BMD) before and after a 5-year hormone replacement therapy (HRT) in 316 early postmenopausal women participating in a randomized controlled trial nested in the population-based Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study. The participants were randomized into two treatment groups: the HRT group (n = 146) received a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate and calcium lactate, 500 mg/day (equal to 93 mg Ca2+) alone or in combination with vitamin D3, 100-300 IU/day. The non-HRT group (n = 170) received calcium lactate, 500 mg alone or in combination with vitamin D3, 100-300 IU/day. BMDs of the lumbar spine (L2-4) and proximal femur were measured by using dual X-ray absorptiometry (DXA). The frequency of Leu7/Pro7 polymorphism was 15.2%. At baseline, there were no significant differences in the lumbar or femoral neck BMD between the subjects who had Leu7Pro7 polymorphism and the normal subjects. After 5 years, the BMD of the femoral neck remained unaltered and that of the lumbar spine increased by 1.7% in the HRT group, whereas both BMDs were decreased by 4-5% in the non-HRT group. After 5 years, the femoral neck BMD was significantly lower in those with the wild-type NPY polymorphism than in those with Leu7/Pro7 polymorphism (P = 0.040) in the non-HRT group. In the HRT group, the changes in BMD were quite modest and not significantly modified by Leu7/Pro7 genotype. We conclude that the Leu7/Pro7 polymorphism in NPY signal gene may favorably affect femoral neck BMD in postmenopausal women.