Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy.

BACKGROUND: Hyperlipidaemia is a major risk factor for cardiovascular disease, and atherosclerosis is the underlying cause of both myocardial infarction and stroke. We have previously shown that the Pro251 variant of perilipin-2 reduces plasma triglycerides and may therefore be beneficial to reduce atherosclerosis development. OBJECTIVE: We sought to delineate putative beneficial effects of the Pro251 variant of perlipin-2 on subclinical atherosclerosis and the mechanism by which it acts. METHODS: A pan-European cohort of high-risk individuals where carotid intima-media thickness has been assessed was adopted. Human primary monocyte-derived macrophages were prepared from whole blood from individuals recruited by perilipin-2 genotype or from buffy coats from the Karolinska University hospital blood central. RESULTS: The Pro251 variant of perilipin-2 is associated with decreased intima-media thickness at baseline and over 30 months of follow-up. Using human primary monocyte-derived macrophages from carriers of the beneficial Pro251 variant, we show that this variant increases autophagy activity, cholesterol efflux and a controlled inflammatory response. Through extensive mechanistic studies, we demonstrate that increase in autophagy activity is accompanied with an increase in liver-X-receptor (LXR) activity and that LXR and autophagy reciprocally activate each other in a feed-forward loop, regulated by CYP27A1 and 27OH-cholesterol. CONCLUSIONS: For the first time, we show that perilipin-2 affects susceptibility to human atherosclerosis through activation of autophagy and stimulation of cholesterol efflux. We demonstrate that perilipin-2 modulates levels of the LXR ligand 27OH-cholesterol and initiates a feed-forward loop where LXR and autophagy reciprocally activate each other; the mechanism by which perilipin-2 exerts its beneficial effects on subclinical atherosclerosis.

Particulate matter air pollution components and risk for lung cancer.

BACKGROUND: Particulate matter (PM) air pollution is a human lung carcinogen; however, the components responsible have not been identified. We assessed the associations between PM components and lung cancer incidence. METHODS: We used data from 14 cohort studies in eight European countries. We geocoded baseline addresses and assessed air pollution with land-use regression models for eight elements (Cu, Fe, K, Ni, S, Si, V and Zn) in size fractions of PM2.5 and PM10. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effect models for meta-analysis. RESULTS: The 245,782 cohort members contributed 3,229,220 person-years at risk. During follow-up (mean, 13.1 years), 1878 incident cases of lung cancer were diagnosed. In the meta-analyses, elevated hazard ratios (HRs) for lung cancer were associated with all elements except V; none was statistically significant. In analyses restricted to participants who did not change residence during follow-up, statistically significant associations were found for PM2.5 Cu (HR, 1.25; 95% CI, 1.01-1.53 per 5 ng/m(3)), PM10 Zn (1.28; 1.02-1.59 per 20 ng/m(3)), PM10 S (1.58; 1.03-2.44 per 200 ng/m(3)), PM10 Ni (1.59; 1.12-2.26 per 2 ng/m(3)) and PM10 K (1.17; 1.02-1.33 per 100 ng/m(3)). In two-pollutant models, associations between PM10 and PM2.5 and lung cancer were largely explained by PM2.5 S. CONCLUSIONS: This study indicates that the association between PM in air pollution and lung cancer can be attributed to various PM components and sources. PM containing S and Ni might be particularly important.

Prediction of cardiovascular disease by abdominal obesity measures is dependent on body weight and sex--results from two community based cohort studies.

AIM: To study waist-hip ratio (WHR), waist circumference (WC), sagittal abdominal diameter (SAD), and waist-hip-height ratio (WHHR) as predictors of CVD, in men and women stratified by BMI (cut-off ≥25). METHODS AND RESULTS: A cohort of n = 3741 (53% women) 60-year old individuals without CVD was followed for 11-years (375 CVD cases). To replicate the results, we also assessed another large independent cohort; The Malmö Diet and Cancer study - cardiovascular cohort (MDCC, (n = 5180, 60% women, 602 CVD cases during 16-years). After adjustment for established risk factors in normal-weight women, the hazard ratio (HR) per one standard deviation (SD) were; WHR; 1.91 (95% confidence interval (CI) 1.35-2.70), WC; 1.81 (95% CI 1.02-3.20), SAD; 1.25 (95% CI 0.74-2.11), and WHHR; 1.97 (95% CI 1.40-2.78). In men the association with WHR, WHHR and WC were not significant, whereas SAD was the only measure that significantly predicted CVD in men (HR 1.19 (95% CI 1.04-1.35). After adjustments for established risk factors in overweight/obese women, none of the measures were significantly associated with CVD risk. In men, however, all measures were significant predictors; WHR; 1.24 (955 CI 1.04-1.47), WC 1.19 (95% CI 1.00-1.42), SAD 1.21 (95% CI 1.00-1.46), and WHHR; 1.23 (95% CI 1.05-1.44). Only the findings in men with BMI ≥ 25 were verified in MDCC. CONCLUSION: In normal weight individuals, WHHR and WHR were the best predictors in women, whereas SAD was the only independent predictor in men. Among overweight/obese individuals all measures failed to predict CVD in women, whereas WHHR was the strongest predictor after adjustments for CVD risk factors in men.

The association between plasma homocysteine and coronary heart disease is modified by the MTHFR 677C>T polymorphism.

OBJECTIVE: An elevated level of total plasma homocysteine (tHcy) has been associated with risk of coronary heart disease (CHD). The level of tHcy is affected by lifestyle, in addition to genetic predisposition. The methylene tetrahydrofolate reductase (MTHFR) 677C>T polymorphism (rs1801133) is among the strongest genetic predictors of tHcy. We examined whether the association between tHcy and CHD is modified by the MTHFR 677C>T polymorphism. DESIGN AND SETTING: Data from two case-control studies of first-time myocardial infarction (MI), Stockholm Heart Epidemiology Programme (SHEEP), and for MI and unstable angina, INTERGENE, were analysed in parallel. PATIENTS: THcy was determined in a total of 1150 cases and 1753 controls. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The outcome comprised first-time MI and unstable angina, subsumed as CHD. Logistic regression was used to investigate the association between tHcy and CHD, and its modification by genotype. RESULTS: High tHcy was confirmed to be a risk factor for CHD in both studies. In SHEEP, the association between tHcy and MI was observed in MTHFR 677 C-homozygotes (OR=1.4, 95% CI 1.2 to 1.6, for a difference by 1 SD of log tHcy) and in heterozygotes (OR=1.3, 95% CI 1.1 to 1.6) but not in T-homozygotes, independent of smoking, physical activity and obesity. An effect modification of similar magnitude was observed but not statistically significant in the smaller INTERGENE study, and confirmed in a meta-analysis of both studies. CONCLUSIONS: Two Swedish case-control studies showed that the association between elevated tHcy and CHD was confined to carriers of the MTHFR 677 C-allele, which could have implications for the efficiency of tHcy-lowering treatment.

Novel and established anthropometric measures and the prediction of incident cardiovascular disease: a cohort study.

OBJECTIVES: The aim of this study was to compare novel and established anthropometrical measures in their ability to predict cardiovascular disease (CVD), and to determine whether they improve risk prediction beyond classical risk factors in a cohort study of 60-year-old men and women. We also stratified the results according to gender to identify possible differences between men and women. Furthermore, we aimed to replicate our findings in a large independent cohort (The Malmö Diet and Cancer study-cardiovascular cohort). METHODS: This was a population-based study of 1751 men and 1990 women, aged 60 years and without CVD at baseline, with 375 incident cases of CVD during 11 years of follow-up. Weight, height, waist circumference (WC), hip circumference and sagittal abdominal diameter (SAD) were measured at baseline. Body mass index (BMI), waist-hip ratio (WHR), waist-hip-height ratio (WHHR), WC-to-height ratio (WCHR) and SAD-to-height ratio (SADHR) were calculated. RESULTS: All anthropometric measures predicted CVD in unadjusted Cox regression models per s.d. increment (hazard ratios, 95% confidence interval), while significant associations after adjustments for established risk CVD factors were noted for WHHR 1.20 (1.08-1.33), WHR 1.14 (1.02-1.28), SAD 1.13 (1.02-1.25) and SADHR 1.17 (1.06-1.28). WHHR had higher increases in C-statistics, and model improvements (likelihood ratio tests (P<0.001)). In the replication study (MDC-CC, n=5180), WHHR was the only measure that improved Cox regression models in men (P=0.01). CONCLUSION: WHHR, a new measure reflecting body fat distribution, showed the highest risk estimates after adjustments for established CVD risk factors. These findings were verified in men but not women in an independent cohort.

LDL oxidative modification and carotid atherosclerosis: results of a multicenter study.

OBJECTIVE: Serum LDL conjugated diene concentration is a marker of oxidative modification of LDL. We investigated the relationship between LDL conjugated dienes and cross-sectional subclinical atherosclerosis assessed by carotid IMT in high-risk subjects of a multicenter study. METHODS: Serum LDL conjugated dienes and ultrasonographically assessed carotid intima-media thickness (IMT(mean), IMT(max) and IMT(mean-max)) were available for 553 subjects from Finland, France, Italy, the Netherlands, and Sweden. RESULTS: In multivariate regression analysis, gender (p < 0.001), age (p < 0.001), systolic blood pressure (IMT(mean), p = 0.01; IMT(mean-max), p = 0.05) and serum LDL conjugated dienes (p = 0.02 for both IMT(mean) and IMT(mean-max)) were the strongest determinants of IMT variation, adjusted for study center, ultrasound videotape reader and serum LDL cholesterol. Pack-years of smoking, added into the regression model, did not destroy the significant association between increased serum LDL conjugated dienes and IMT. Ratio of LDL conjugated dienes to LDL particle cholesterol was higher in subjects of Northern recruiting centers than of Southern centers (r = 0.39, p < 0.0001). CONCLUSIONS: There was a cross-sectional association between in vivo increased LDL oxidative modification and subclinical atherosclerosis after adjustment for traditional risk factors. The subjects in Northern countries of Europe had more oxidatively modified lipids per cholesterol in LDL particle than subjects in Southern countries.

Telomere length and cardiovascular risk in hypertensive patients with left ventricular hypertrophy: the LIFE study.

Short telomeres are associated with aging and age-related diseases. Our aim was to determine whether short leukocyte telomere length is associated with risk factors and cardiovascular diseases in a high-risk hypertensive population. We measured leukocyte telomere lengths at recruitment in 1271 subjects with hypertension and left ventricular hypertrophy (LVH) participating in the Lifestyle Interventions and Independence for Elders (LIFE) study. At baseline, short mean telomere length was associated with coronary artery disease in males (odds ratio (OR) 0.61, 95% confidence interval (CI) 0.39-0.95), and transient ischemic attack in females (OR 0.62 95% CI 0.39-0.99). Proportion of short telomeres (shorter than 5 kb) was associated with Framingham risk score (r=0.07, P<0.05), cerebrovascular disease (OR 1.18, 95% CI 1.01-1.15) and type 2 diabetes in men (OR 1.07, 95% CI 1.02-1.11). During follow-up, proportion of short telomeres was associated with combined cardiovascular mortality, stroke or angina pectoris (hazard ratio 1.04, 95% CI 1.01-1.07). Telomere length was not associated with smoking, body mass index, pulse pressure or self-reported use of alcohol. Our data suggest that reduced leukocyte telomere length is associated with cardiovascular risk factors and diseases as well as type 2 diabetes, and is a predictor of cardiovascular disease in elderly patients with hypertension and LVH.

Genetic variants of TNFSF4 and risk for carotid artery disease and stroke.

In two independent human cohorts, the minor allele of SNP rs3850641 in TNFSF4 was significantly more frequent in individuals with myocardial infarction than in controls. In mice, Tnfsf4 expression is associated with increased atherosclerosis. The expression of TNFSF4 in human atherosclerosis and the association between genotype and cerebrovascular disease have not yet been investigated. TNFSF4 messenger RNA (mRNA) levels were significantly higher in human atherosclerotic lesions compared with controls (730 +/- 30 vs 330 +/- 65 arbitrary units, p < 0.01). TNFSF4 was mainly expressed by macrophages in atherosclerotic lesions. In cell culture, endothelial cells upregulated TNFSF4 in response to tumor necrosis factor alpha (TNF-alpha; 460 +/- 110 vs 133 +/- 8 arbitrary units, p < 0.001 after 6 h of stimulation). We analyzed the TNFSF4 gene in 239 patients who had undergone carotid endarterectomy and 138 matching controls from The Biobank of Karolinska Carotid Endarterectomies and Stockholm Heart Epidemiology Program cohorts and 929 patients and 1,382 matching controls from the Sahlgrenska Academy Study on Ischemic Stroke and Case Control Study of Stroke cohorts, limiting inclusion to patients with ischemic stroke. Participants were genotyped for the rs3850641 SNP in TNFSF4. Genotype associations were neither found with TNFSF4 mRNA levels nor with atherosclerosis associated systemic factors or risk for stroke. This study shows that TNFSF4 is expressed on antigen-presenting cells in human carotid atherosclerotic lesions but provides no evidence for an association of TNFSF4 gene variation with the risk for ischemic stroke.

Endothelial function and markers of endothelial activation in relation to cardiovascular disease in systemic lupus erythematosus.

OBJECTIVE: Cardiovascular disease (CVD) is common in patients with systemic lupus erythematosus (SLE) although it is not clear whether an increased risk of CVD is a general feature of SLE or whether it applies only to a subgroup of patients. Our objective was to evaluate endothelial function and markers of endothelial activation in relation to CVD in SLE. METHODS: Twenty-six women with SLE and previous CVD (SLE/CVD cases, defined as objectively verified angina pectoris, myocardial infarction, cerebral infarction, or intermittent claudication; 52+/-8.2 years) were compared with age-matched SLE women without CVD (SLE controls) and population control women. Flow-mediated dilatation (FMD) of the brachial artery after reactive hyperaemia and nitroglycerin-mediated dilatation (NMD) after sublingual nitroglycerin administration were determined by ultrasound. Soluble thrombomodulin (sTM) and soluble vascular cellular adhesion molecule-1 (sVCAM-1) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: FMD and NMD levels did not differ between SLE controls and population controls. In SLE cases FMD and NMD were not assessed because of interference with nitro-related medication. sVCAM-1 discriminated between SLE cases, SLE controls, and population controls (ng/mL; 814+/-221 vs. 545+/-214 vs. 401+/-189, p<0.01), whereas sTM (ng/mL; 5.2+/-2.8 vs. 4.2+/-1.9 vs. 3.0+/-0.5) differed between both SLE groups and controls (p<0.05). CONCLUSION: In this study SLE women free of CVD had good endothelial function (FMD), a possible marker of protection from lupus-related CVD. In addition, high levels of sVCAM-1, associated with systemic tumour necrosis factor-alpha (TNFalpha) activity, were identified as a novel discriminator for SLE-related CVD. This supports our hypothesis that SLE patients with enhanced systemic TNFalpha activity are at high risk of developing CVD.

Blood markers of inflammation and coagulation and exposure to airborne particles in employees in the Stockholm underground.

OBJECTIVES: Although associations have been found between levels of ambient airborne particles and cardiovascular disease (CVD) in the general population, little is known about possible cardiovascular effects from high exposure to particles in underground railway systems. This study investigates risk markers for CVD in employees exposed to particles in the Stockholm underground system. METHODS: 79 workers (54 men and 25 women) in the Stockholm underground were investigated between November 2004 and March 2005. All were non-smokers aged 25-50 years. Three exposure groups were delineated: 29 platform workers with high exposure to particles, 29 train drivers with medium exposure and 21 ticket sellers with low exposure (control group). A baseline blood sample was taken after 2 non-working days, and a second sample after 2 working days, for analysis of levels of plasminogen activator inhibitor-1 (PAI-1), high-sensitivity C-reactive protein (hs-CRP), interleukin-6, fibrinogen, von Willebrand factor and factor VII. The study investigated changes in plasma concentrations between sample 1 and sample 2, and differences in average concentrations between the groups. RESULTS: No changes between sample 1 and 2 were found that could be attributed to particle exposure. However, the highly exposed platform workers were found to have higher plasma concentrations of PAI-1 and hs-CRP than the ticket sellers and train drivers. This suggests that particle exposure could have a long-term inflammatory effect. These differences remained for PAI-1 in the comparison between platform workers and ticket sellers after adjusting for body mass index. CONCLUSIONS: Employees who were highly exposed to airborne particles in the Stockholm underground tended to have elevated levels of risk markers for CVD relative to employees with low exposure. However, the differences observed cannot definitely be linked to particle exposure as such.

Cystatin C--a marker of peripheral atherosclerotic disease?

UNLABELLED: It has been suggested that Cystatin C, besides its function as a marker of glomerular filtration, could be an independent marker of cardiovascular disease. However, studies on this topic are few and results have been indecisive. Our aim was to further investigate the subject of Cystatin C as an independent marker of peripheral atherosclerotic disease. METHOD: Blood samples were analysed for serum Cystatin C, IL6, CRP and creatinine in 103 males with peripheral arterial disease (PAD) and 96 controls matched for age and sex. Creatinine clearance (CCr) was calculated according to Cockcroft's formula and estimated glomerular filtration rate (eGFR) was calculated according to MDRD formula. RESULTS: Cystatin C-concentration was higher in PAD-patients compared to controls; 1.09+/-0.40 vs. 0.95+/-0.17 mg/L (p<0.01). There was no difference in CCr; 81+/-27 vs. 82+/-22 mL/min or eGFR; 76+/-21 vs. 79+/-14 mL/min. Cystatin C correlated to CCr, logIL-6 and logCRP in both patients (r=-0.60, p<0.001), (r=0.35, p<0.001) and (r=0.30, p<0.01) and controls (-0.44, p<0.001), (0.38, p<0.001) and (r=0.32, p<0.01), respectively. In an analysis of covariance, corrected for difference in eGFR, Cystatin C remained higher in PAD-patients compared to controls; 1.09 (C.I. 1.04-1.14) vs. 0.96 (C.I. 0.90-1.01). CONCLUSION: Cystatin C-concentration, corrected for differences in eGFR, IL-6 and CRP values, is higher in PAD-patients compared to controls. Our finding suggests that Cystatin C may be an independent marker of atherosclerotic disease apart from its relation to kidney function.

The metabolic syndrome: prevalence and association to leisure-time and work-related physical activity in 60-year-old men and women.

BACKGROUND AND AIM: This study examined the prevalence of the metabolic syndrome and its association to lifestyle factors in 60-year-old men and women, with special emphasis on physical activity (PA). METHODS AND RESULTS: Every third 60-year-old man and woman in the Stockholm County, Sweden, was invited to a survey of cardiovascular risk factors. Seventy-seven percent of the sample, 4228 individuals, agreed to participate (2036 men and 2192 women). Participants underwent physical examination and laboratory tests, and completed a questionnaire. After excluding 364 subjects suffering from cardiovascular disease and/or cancer, the prevalence of the metabolic syndrome was 24% and 19% in men and women, respectively. The adjusted odds ratio for having the metabolic syndrome in the high leisure-time PA group was 0.33 (95% confidence interval: 0.22-0.51) using the low leisure-time PA group as reference. However, no such inverse association was noted for work-related PA. CONCLUSIONS: This cross-sectional survey of 60-year-old men and women demonstrates a high prevalence of the metabolic syndrome. The robust inverse dose-response relationship between leisure-time PA and the metabolic syndrome emphasises the role of PA in the prevention and treatment of the metabolic syndrome.

The association between fibrinogen haplotypes and myocardial infarction in men is partly mediated through pleiotropic effects on the serum IL-6 concentration.

BACKGROUND AND OBJECTIVES: Fibrinogen haplotypes have been associated with risk of myocardial infarction (MI), independently of plasma fibrinogen concentration, and experimental data indicate that fibrinogen exerts pleiotropic effects on interleukin 6 (IL-6) production. Also, the coagulation factor XIII (gene symbol F13A1) Val34Leu haplotype tag single nucleotide polymorphism (htSNP) has been reported to exert pleiotropic effects on serum IL-6 concentration and to be associated with risk of MI. Therefore, in the present case-control study (a substudy to the Stockholm Heart Epidemiology Program), the effects of the fibrinogen gamma (FGG) 9340T>C [rs1049636], fibrinogen alpha (FGA) 2224G>A [rs2070011] and F13A1 Val34Leu [rs5985] htSNPs on concentrations of plasma fibrinogen and serum IL-6 and risk of MI were assessed. RESULTS: There were no associations between these SNPs and the plasma fibrinogen concentration. In contrast, in male controls the FGA 2224G>A htSNP was significantly associated with serum IL-6 concentration (P < 0.05). Also, in men the FGG-FGA*1 haplotype (containing the major FGG 9340T and FGA 2224G alleles) was associated with increased risk of MI [adjusted odds ratio (OR) 95% confidence interval (CI): 1.29 (1.02, 1.62)] and with higher IL-6 concentrations, whereas the least common FGG-FGA*4 haplotype (containing the minor FGG 9340C and FGA 2224A alleles) conferred lowered risk [adjusted OR (95% CI): 0.70 (0.57, 0.86)] and lowered IL-6 concentrations. In women, fibrinogen haplotypes were not associated with risk of MI after adjusting for cardiovascular risk factors. CONCLUSION: In healthy men, fibrinogen haplotypes are associated with serum IL-6 concentrations in a manner consistent with their impact on MI risk.

Association of TNF-alpha serum levels and TNFA promoter polymorphisms with risk of myocardial infarction.

Elevated levels of tumor necrosis factor-alpha (TNF-alpha), and presence of polymorphisms of the TNFA gene have been implicated in cardiovascular disease pathogenesis. We explored the relationship between polymorphisms in the TNFA gene (-1031C/T, -863C/A -857T/C, -308G/A, -238G/A), protein levels of TNF-alpha and their association to myocardial infarction (MI) using a sample of 1213 post-MI patients and 1561 healthy controls. MI risk was higher among men with elevated TNF-alpha levels, with the highest compared to the lowest TNF-alpha quartile giving a 70% risk increase (OR [95% CI]: 1.7 [1.1; 2.6]). Obese subjects who also had elevated TNF-alpha levels were at even higher risk for MI (OR [95% CI]: 3.4 [2.1; 5.6]). Higher TNF-alpha levels were seen among smokers (but not among non-smokers) carrying the -857T allele. Furthermore, a rare haplotype occurred more frequently among the cases than the controls. Elevated TNF-alpha levels are associated with increased MI risk. Obese subjects with elevated TNF-a levels, and carriers of polymorphisms in or near TNFA are particularly susceptible to the hazards of smoking, results which may have implications for cardiovascular preventive measures.

Increased risk of heart failure as a consequence of perioperative myocardial injury after coronary artery bypass grafting.

OBJECTIVE: To analyse the relation between perioperative myocardial injury (PMI) and the risk of subsequent heart failure after coronary artery bypass grafting (CABG). DESIGN AND SETTING: Clinical data were documented prospectively in all patients and stored in a computer. All hospital readmissions were identified and the registered primary diagnoses were analysed. Survival information on all patients was obtained by use of combined registers. The study was carried out at the cardiac surgical referral centre of University Hospital, Uppsala, Sweden. PATIENTS: 7493 patients discharged alive after primary CABG between 1987 and 1996 were followed up until the first hospital readmission for heart failure, death, or 31 December 1996 was reached. MAIN OUTCOME MEASURES: Hospital readmission for heart failure or late mortality. RESULTS: Of the patients studied 576 (7.7%) were readmitted for heart failure. Actuarial freedom from readmission for heart failure after four years was 93%, and after seven years, 89%. Of the 576 patients, 114 (20%) had had PMI, which increased the risk of heart failure independently (hazard ratio (HR) 2.3, 95% confidence interval (CI) 1.8 to 2.8). Increased age, female sex, diabetes, previous myocardial infarction, dyspnoea, preoperative atrial fibrillation, left ventricular dysfunction, and triple vessel disease were independent risk factors for heart failure. The use of an internal mammary artery decreased the risk. PMI implied increased mortality (HR 1.4, 95% CI 1.1 to 1.8). Late mortality was greatly increased in patients readmitted for heart failure. CONCLUSION: PMI increased the risk of heart failure and late death after CABG, and heart failure had a notable adverse effect on late survival.

The relation between alcohol intake and physical activity and the fatty acids 14 : 0, 15 : 0 and 17 : 0 in serum phospholipids and adipose tissue used as markers for dairy fat intake.

The relative contents of the fatty acids 14 : 0, 15 : 0 and 17 : 0 in serum and adipose tissue may be used as biological markers of dairy fat intake. However, the determinants of these fatty acids are not fully understood. This study investigates the relationship between these fatty acids and the intake of macronutrients and physical activity in a cross-sectional study of 301 healthy men aged 61-64 years. Dietary intake was assessed using a pre-coded 7 d food record, and physical activity during the previous year was recorded in an interview. Under-reporters of energy intake were identified by the Goldberg cut-off. Fatty acid composition was determined in serum phospholipids (PL) and subcutaneous adipose tissue (AT) from the upper buttock. The relative content of each of 14 : 0, 15 : 0 and 17 : 0 in PL and AT was positively associated with the intake of dairy fat. In addition, all three fatty acids were inversely correlated with alcohol intake, R ranging from -0.28 to -0.53 (P<0.001). The results were not markedly affected when under-reporters (n 88) were excluded from the analyses. In both PL and AT, the relative content of the fatty acids was approximately 5% higher in a group of high physical activity compared with a group of low physical activity, although significant trends were only seen for 14 : 0 in PL and 17 : 0 in AT. The findings suggest that adjustments should be made for alcohol intake when the fatty acids 14 : 0, 15 : 0 and 17 : 0 are applied as markers for dairy fat intake.

Alcohol consumption and cardiovascular risk in hypertensives with left ventricular hypertrophy: the LIFE study.

The Losartan Intervention For End point reduction in hypertension (LIFE) study showed superiority of losartan over atenolol for reduction of composite risk of cardiovascular death, stroke, and myocardial infarction in hypertensives with left ventricular hypertrophy. We compared hazard ratios (HR) in 4287 and 685 participants who reported intakes of 1-7 and >8 drinks/week at baseline, respectively, with those in 4216 abstainers, adjusting for gender, age, smoking, exercise, and race. Within categories, clinical baseline characteristics, numbers randomized to losartan and atenolol, and blood pressure (BP) lowering were similar on the drug regimens. Overall BP control (<140/90 mmHg) at end of follow-up was similar in the categories. Composite end point rate was lower with 1-7 (24/1000 years; HR 0.87, P<0.05) and >8 drinks/week (26/1000 years; HR 0.80, NS) than in abstainers (27/1000 years). Myocardial infarction risk was reduced in both drinking categories (HR 0.76, P<0.05 and HR 0.29, P<0.001, respectively), while stroke risk tended to increase with >8 drinks/week (HR 1.21, NS). Composite risk was significantly reduced with losartan compared to atenolol only in abstainers (HR 0.81 95% confidence interval, CI (0.68, 0.96), P<0.05), while benefits for stroke risk reduction were similar among participants consuming 1-7 drinks/week (HR 0.73, P<0.05) and abstainers (HR 0.72, P<0.01). Despite different treatment benefits, alcohol-treatment interactions were nonsignificant. In conclusion, moderate alcohol consumption does not change the marked stroke risk reduction with losartan compared to atenolol in high-risk hypertensives. Alcohol reduces the risk of myocardial infarction, while the risk of stroke tends to increase with high intake.

TNF-alpha: a link between hypertriglyceridaemia and inflammation in SLE patients with cardiovascular disease.

Patients with systemic lupus erythematosus (SLE) are at high risk of cardiovascular disease (CVD). Tumour necrosis factor-alpha (TNF-alpha) has been implicated in the pathophysiological processes of both SLE and CVD. This study focuses on the role of TNF-alpha and its soluble receptors in SLE-related CVD. In summary, 26 women (52 +/- 8.2 years) with SLE and a history of CVD (SLE cases) we compared with 26 age-matched women with SLE and no clinical manifestations of CVD (SLE controls) and 26 age-matched population-based control women (population controls). Plasma concentrations of circulating TNF-alpha, TNF-alpha receptor 1 (sTNFR1) and TNF-a receptor 2 (sTNFR2) were determined by ELISA. TNF-alpha, sTNFR1 and sTNFR2 were raised in SLE cases as compared to SLE controls (P = 0.009; P = 0.001; P = 0.001, respectively), and SLE controls had higher levels than population controls (P = 0.001; P = 0.02; P = 0.001, respectively). Exclusively in the SLE case group there was a striking positive correlation between TNF-alpha and plasma triglycerides (r = 0.57, P < 0.002), VLDL triglycerides (r = 0.54, P = 0.004) and VLDL cholesterol (r = 0.58, P = 0.002). Furthermore, TNF-alpha correlated with the waist-hip ratio but not with estimated insulin resistance. TNF-alpha may thus be a major factor in SLE-related CVD acting both by contributing to hypertriglyceridaemia and by promoting atherosclerosis-related inflammation. sTNFR1 and sTNFR2 are strongly associated with CVD in SLE but their exact roles in disease development remain to be elucidated.

Low prevalence of the metabolic syndrome in wine drinkers--is it the alcohol beverage or the lifestyle?

OBJECTIVE: To study how the intake of alcohol and the choice of wine, beer, and spirits is related to lifestyle factors and the metabolic syndrome in 60-y-old men and women. DESIGN: Cross-sectional population based study. SETTING: Stockholm County, Sweden. SUBJECTS: Sixty-year-old men and women (n=4232). RESULTS: Moderate intake of wine (10-30 g/day) was associated with a lifestyle characterized by being married, having a university education, being employed, being Swedish-born, having a good quality of life according to economy, leisure time and health, compared with a group with low alcohol intake. The opposite characteristics were seen among the non-drinkers. Drinkers of spirits were more often smokers and also reported higher intake of sausage and fried potatoes compared with a group with low alcohol intake. In women, the metabolic syndrome was significantly more common in non-drinkers (20%), P<0.05, and less common among wine drinkers (8%), P<0.01, compared with a group with low alcohol intake. After adjustments, a significant lower odds ratio for the metabolic syndrome were seen in wine drinkers in women (OR=0.60, P<0.05). CONCLUSIONS: Compared with low alcohol drinkers, moderate wine drinkers exhibited a more favorable pattern according to both lifestyle factors and metabolic parameters. The close link between alcohol drinking behaviour and lifestyle habits illustrate the complex relationship between alcohol and health.

The G-455A polymorphism of the fibrinogen Bbeta-gene relates to plasma fibrinogen in male cases, but does not interact with environmental factors in causing myocardial infarction in either men or women.

OBJECTIVES: To elucidate the association between a genetic polymorphism of the fibrinogen Bbeta-gene (G-455A) and plasma fibrinogen levels and myocardial infarction (MI), respectively. In addition, to explore potential synergistic gene-environment interactions involving this polymorphism--until now, these data were unavailable. DESIGN SETTING AND SUBJECTS: This case-referent study of subjects aged 45-70 and living in Stockholm includes 834 men and 346 women with first-time MI and 1034 men and 494 women randomly chosen as referents from the population. The cases were identified between 1992 and 1994 at the 10 emergency hospitals in Stockholm County. MAIN OUTCOME MEASURES: MI and plasma fibrinogen levels. RESULTS: Crude analyses associated a high level of plasma fibrinogen with an increased risk of MI in both men and women. However, the relative risk decreased after controlling for other risk factors. The multivariate-adjusted odds ratio (OR) (95% confidence interval) was 1.6 (1.2-2.3) for men and 1.5 (0.9-2.6) for women. Presence of the A allele at the G-455A polymorphic site indicated higher plasma fibrinogen levels than the presence of the G allele, but the difference was only statistically significant for male cases. The -455A allele was not associated with an increased risk of MI. Furthermore, there were no strong indications of synergistic interaction between the G-455A polymorphism and any of the environmental exposures considered. CONCLUSIONS: In this large number of MI cases and referents, a high level of plasma fibrinogen was independently associated with increased risk of MI in men but not in women. The presence of the A allele at the G-455A polymorphism of the fibrinogen Bbeta-gene was not associated with increased risk of MI, and no synergistic gene-environment interactions were detected.