Serum carotenoids, alpha-tocopherol and mortality risk in a prospective study among Dutch elderly

Background Although beta -carotene has shown inverse associations with chronic diseases involving free radical damage in observational epidemiological studies less attention has been paid to five other major carotenoids also showing antioxidant activity irt vitro. Methods We studied the associations between 7.2-year mortality and serum levels of six caroteneids, and alpha -tocopherol, measured in stored serum, sampled in 1991/1992 during a health survey among 638 independently Living elderly subjects aged 65-85 years. Proportional hazards regression was used to estimate hazard ratios of all-cause mortality for the lowest tertiles of serum vitamins with the highest tertiles, adjusting for possible confounding effects. Results During a follow-up period of 7.2 years 171 elderly died. The adjusted hazard ratios for ail-cause mortality for the lowest tertiles of vitamins compared with the highest tertiles were between 1.02 and 1.73. The strongest increase in mortality risk was seen for beta -cryptoxanthin (1.52, 95% CI: 1.00, 2.32), lutein (1.56, 95% CI : 1.05, 2.31) and zeaxanthin (1.32, 95% CI : 0.89, 1.97) and their sum (oxygenated carotenoids: 1.73, 95% CI: 1.12, 2.67). Tests for trend were significant (P <0.05) for all-cause mortality risk and serum levels of total carotenoids, oxygenated carotenoids and -cryptoxanthin. Conclusions Our findings suggest that serum levels of individual carotenoids, particularly the oxygenated species are inversely associated with all-cause mortality and should be considered as candidates for further investigations

Expression of type III hyperlipoproteinemia in apolipoprotein E2 (Arg158 --> Cys) homozygotes is associated with hyperinsulinemia

Type III hyperlipoproteinemia (HLP) is mainly found in homozygous carriers of apolipoprotein E2 (apoE2, Arg158-->Cys). Only a small percentage (< 5%) of these apoE2 homozygotes develops hyperlipidemia, indicating that additional environmental and genetic factors contribute to the expression of type III HLP. In the present study, first, the prevalence of type III HLP among apoE2 homozygotes was estimated in a Dutch population sample of 8888 participants. Second, 68 normocholesterolemic and 162 hypercholesterolemic apoE2 homozygotes (type III HLP patients) were collected to investigate additional factors influencing type III HLP expression. In the Dutch population sample, apoE2 homozygosity occurred with a frequency of 0.6% (57 of 8888 individuals). Among the 57 E2/2 subjects, 10 type III HLP patients were identified (prevalence 18%). Comparison of normocholesterolemic E2/2 subjects and type III HLP patients showed that the latter had a significantly increased body mass index (25.6 +/- 4.0 versus 26.9 +/- 3.8 kg/m(2), respectively; P=0.03) and prevalence of hyperinsulinemia (26% versus 63%, respectively; P<0.001). Multiple linear regression analysis

High-density lipoprotein cholesterol subfractions HDL2 and HDL3 are reduced in women with rheumatoid arthritis and may augment the cardiovascular risk of women with RA: a cross-sectional study

Contains fulltext : 108119.pdf (publisher's version ) (Open Access)INTRODUCTION: Higher levels of high density lipoprotein (HDL) subfractions HDL3-chol and particularly HDL2-chol protect against cardiovascular disease (CVD), but inflammation reduces the HDL level and may impair its anti-atherogenic effect. Changed HDL composition through the impact of inflammation on HDL subfractions may contribute to the excess risk of CVD in rheumatoid arthritis (RA). In this study, we investigated whether HDL2-chol and HDL3-chol concentrations differ between RA patients and healthy controls, and whether these levels are related to the level of RA disease activity. METHODS: Non-fasting blood samples were collected from 45 RA patients and 45 healthy controls. None of the participants had a history of CVD, diabetes, or used lipid-lowering drugs. HDL2-chol and HDL3-chol concentrations were obtained by ultracentrifugation. Regression modeling was used to compare HDL subfraction levels between RA patients and healthy controls, and to analyze the effect of disease activity on HDL2-chol and HDL3-chol. RESULTS: HDL2-chol and HDL3-chol were significantly lower in RA patients compared to healthy controls (P = 0.01, P = 0.005, respectively). The HDL2:HDL3 ratio was significantly lower in patients compared to controls (P = 0.04). Reduced HDL2-chol and HDL3-chol levels were primarily present in female RA patients and not in male RA patients. A modest effect of the disease activity score in 28 joins ( DAS28) on HDL2-chol concentrations was found, after correction for disease duration, glucocorticosteroid use and body mass index (BMI), with a 0.06 mmol/L decrease with every point increase in DAS28 (P = 0.05). DAS28 did not significantly affect HDL3-chol concentrations (P = 0.186). CONCLUSIONS: Both HDL subfractions but particularly HDL2-chol concentrations were decreased in RA, primarily in women. This seems to be associated with disease activity and is of clinical relevance. The reduction of the HDL subfraction concentrations, particularly the supposedly beneficial HDL2-chol, may negatively impact the cardiovascular risk profile of women with RA

Treatment options for hypertriglyceridemia: from risk reduction to pancreatitis

Item does not contain fulltextWhile there has been considerable focus on the role and treatment of LDL cholesterol levels, a definitive role of triglycerides in the management of cardiovascular disease has been uncertain. Notably, with increasing triglyceride levels, there is a parallel increase in cholesterol levels carried by triglyceride-rich lipoproteins, which has prompted interest in the use of non-HDL cholesterol levels as a tool guiding interventions. Recent studies have provided evidence for an independent role of triglyceride levels as a cardiovascular risk factor, and recently, an Endocrine Society guideline was published for treatment of hypertriglyceridemia. In contrast to the relative uncertainty regarding triglycerides and cardiovascular disease, a role of very high triglyceride levels as a risk factor for pancreatitis has been well known. The present paper summarizes the underlying evidence for a risk role for triglyceride levels in cardiovascular disease and pancreatitis, current treatment recommendations and areas of future research

Smoking characteristics, antioxidant vitamins, and carotid artery wall thickness among life-long smokers

We studied the associations between the common carotid-intima-media thickness (IMT), as a marker of atherosclerosis, and smoking characteristics and antioxidant vitamins among 158 male life-long cardiovascular disease (CVD)-free smokers. An “increased” carotid IMT was defined as the upper 25%. The prevalence of increased IMT was 2.5 times (odds ratio (OR) = 2.5; 95% CI: 1.1, 5.6) higher among smokers inhaling smoke deeply into the lungs than among moderate and non-inhalers. This association decreased when adjusted for other CVD risk factors. Smokers with an increased carotid IMT did not differ significantly in mean antioxidant vitamin intake and status with the remaining group. However, classical CVD risk factors contributed importantly to increased carotid IMT. In our study, depth of inhalation was the only smoking characteristic associated with carotid IMT although attenuated after adjustment for traditional risk factors for CVD. Furthermore, in these life-long smokers not using any vitamin supplements, no associations were found for antioxidant vitamins

Effect of glutathione S-Transferase M1 genotype on progression of atherosclerosis in lifelong male smokers

We hypothesize that smokers with the null genotype for GSTM1 (GSTM1-0), who thus lack the detoxification enzyme glutathione S-transferase mu1, develop atherosclerosis at an increased rate compared to smokers with the positive genotype (GSTM1-1). We used data from a 2-year randomized placebo-controlled trial on the effect of vitamin E on atherosclerosis among 189 male smokers. Progression of atherosclerosis was measured by 2-year change of the common carotid intima media thickness (CCA-IMT) as measured by B-mode ultrasonography. The frequency of GSTM1-0 genotype was 0.5 in both the placebo and the vitamin E group. Smokers with GSTM1-0 genotype had a tendency to higher baseline CCA-IMT values than those with GSTM1-1 (0.97 versus 0.92 mm, P = 0.09). Within the placebo group, more CCA-IMT progression was found for smokers with the GSTM1-0 than for smokers with the GSTM1-1 genotype after adjustment for baseline IMT and major CVD risk factors (0.050 versus -0.002 mm, P = 0.046). In the vitamin E group no effect of GSTM1 genotype on atherosclerosis progression was found. Overall, smokers with GSTM1-0 genotype had a higher mean 2-year progression compared to those with GSTM1-1 as shown by a difference in increase of 0.042 mm (95% CI 0.006; 0.078, P = 0.02). In conclusion, our data suggest that smokers lacking the detoxifying enzyme GST mu1 develop progression of atherosclerosis at an increased rate. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved

Neutrophil superoxide-anion generating capacity in chronic smoking: effect of long-term alpha-tocopherol therapy

We investigated whether long-term alpha-tocopherol therapy in chronic smoking affects superoxide generating capacity of neutrophils ex vivo. To this purpose, we randomly assigned 128 male chronic smokers (37 21 pack years of smoking) to treatment with placebo (n = 64) or alpha-tocopherol (400 IU dL-alpha-tocopherol daily, n = 64). After two years of therapy, we measured phorbol 12-myristate 13 -acetate- induced superoxide production of isolated neutrophils and of diluted whole blood by monitoring reduction of ferricytochrome c and luminol-enhanced peroxidase-catalyzed chemiluminescence. Plasma lipids and lipoproteins were not different between the two treatment groups. As expected, concentrations of alpha-tocopherol in plasma and in low-density lipoproteins were markedly elevated in the supplemented group compared to the placebo group (+ 120%, P <0.0001 and + 83%, P <0.0001, respectively). Consequently, resistance to in vitro oxidation of low-density lipoproteins (reflected by lag time of conjugated diene formation) was higher in the supplemented group than in the placebo group (+ 22%, P <0.0001). Superoxide generating capacity of neutrophils and superoxide production in diluted whole blood did not differ between α-tocopherol and placebo group. It is concluded that in chronic smoking long-term supranormal α-tocopherol intake does not reduce neutrophil superoxide-anion generating capacity, despite large increases in the concentrations of α-tocopherol in plasma and in low-density lipoproteins

Neutrophil superoxide-anion generating capacity in chronic smoking: effect of long-term alpha-tocopherol therapy

We investigated whether long-term alpha-tocopherol therapy in chronic smoking affects superoxide generating capacity of neutrophils ex vivo. To this purpose, we randomly assigned 128 male chronic smokers (37 21 pack years of smoking) to treatment with placebo (n = 64) or alpha-tocopherol (400 IU dL-alpha-tocopherol daily, n = 64). After two years of therapy, we measured phorbol 12-myristate 13 -acetate- induced superoxide production of isolated neutrophils and of diluted whole blood by monitoring reduction of ferricytochrome c and luminol-enhanced peroxidase-catalyzed chemiluminescence. Plasma lipids and lipoproteins were not different between the two treatment groups. As expected, concentrations of alpha-tocopherol in plasma and in low-density lipoproteins were markedly elevated in the supplemented group compared to the placebo group (+ 120%, P <0.0001 and + 83%, P <0.0001, respectively). Consequently, resistance to in vitro oxidation of low-density lipoproteins (reflected by lag time of conjugated diene formation) was higher in the supplemented group than in the placebo group (+ 22%, P <0.0001). Superoxide generating capacity of neutrophils and superoxide production in diluted whole blood did not differ between α-tocopherol and placebo group. It is concluded that in chronic smoking long-term supranormal α-tocopherol intake does not reduce neutrophil superoxide-anion generating capacity, despite large increases in the concentrations of α-tocopherol in plasma and in low-density lipoproteins

Effects of alpha-tocopherol on superoxide production and plasma intercellular adhesion molecule-1 and antibodies to oxidized LDL in chronic smokers

Antioxidants have been postulated to exert beneficial effects in atherosclerosis. Atherosclerosis is associated with raised plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) and autoantibodies against oxidized low-density lipoprotein (oxLDL). It is not known whether antioxidants affect these plasma factors in chronic smokers. In a randomized double-blind placebo-controlled study involving 128 male normolipidemic chronic smokers the effect of a 2-year a-tocopherol treatment (400 IU dL-a-tocopherol daily) on plasma levels of sICAM-1 and autoantibodies against oxLDL was evaluated. In addition, we monitored production of superoxide by leukocytes ex vivo. It was found that compared to nonsmokers (n = 33) plasma levels of IgG but not IgM autoantibodies against oxLDL and concentrations of sICAM-1 in smokers were significantly elevated (30 and 42%, respectively). After supplementation with a-tocopherol concentration of TBARS in plasma and in vitro oxidizability of LDL had decreased, but autoantibodies and sICAM-1 had not changed. Production of superoxide was not different between a-tocopherol- and placebo-treated smokers. It is concluded that in chronic smokers, long-term treatment with a-tocopherol does not normalize the raised levels of sICAM-1 and autoantibodies against oxLDL, both risk factors for initiation or progression of cardiovascular disease, despite a decrease in in vitro oxidizability of LDL