Significant inverse associations of serum n-6 fatty acids with plasma plasminogen activator inhibitor-1.

Epidemiological studies suggested that n-6 fatty acids, especially linoleic acid (LA), have beneficial effects on CHD, whereas some in vitro studies have suggested that n-6 fatty acids, specifically arachidonic acid (AA), may have harmful effects. We examined the association of serum n-6 fatty acids with plasminogen activator inhibitor-1 (PAI-1). A population-based cross-sectional study recruited 926 randomly selected men aged 40-49 years without CVD during 2002-2006 (310 Caucasian, 313 Japanese and 303 Japanese-American men). Plasma PAI-1 was analysed in free form, both active and latent. Serum fatty acids were measured with gas-capillary liquid chromatography. To examine the association between total n-6 fatty acids (including LA and AA) and PAI-1, multivariate regression models were used. After adjusting for confounders, total n-6 fatty acids, LA and AA, were inversely and significantly associated with PAI-1 levels. These associations were consistent across three populations. Among 915 middle-aged men, serum n-6 fatty acids had significant inverse associations with PAI-1.

Differential association of docosahexaenoic and eicosapentaenoic acids with carotid intima-media thickness.

BACKGROUND AND PURPOSE: Recent studies reported the differential effect of docosahexaenoic (DHA) and eicosapentaenoic acids (EPA). We examined the differential association of DHA and EPA with carotid intima-media thickness (IMT) in Japanese individuals in Japan and in U.S. white individuals and explored whether DHA or EPA contributes to the difference in IMT between the two groups. METHODS: A population-based cross-sectional study in 608 Japanese and U.S. white men aged 40 to 49 was conducted to assess IMT, serum DHA, EPA, and other cardiovascular risk factors. RESULTS: Japanese compared to U.S. whites had significantly lower IMT (mean±SD, 618±81 and 672±94 µm for Japanese and whites, respectively; P<0.001) and had >2-fold higher levels of DHA and EPA. DHA, but not EPA, had an inverse association with IMT in both Japanese and U.S. whites. The inverse association remained only in Japanese men after adjusting for risk and other factors. The significant difference in multivariable-adjusted IMT became nonsignificant after further adjusting for DHA (mean difference, 17 µm; 95% CI, -8 to 43; P=0.177) but not EPA. In this multivariable-adjusted model, DHA but not EPA was a significant predictor of IMT (P=-0.032 versus 0.863, respectively). CONCLUSIONS: These data suggest that DHA may have a more potent antiatherogenic effect than EPA, especially in levels observed in the Japanese, independent of risk factors.

Serum n-6 fatty acids and lipoprotein subclasses in middle-aged men: the population-based cross-sectional ERA-JUMP study.

BACKGROUND: The associations of serum omega-6 (n-6) fatty acids with lipoprotein subclasses at the population level are uncertain. OBJECTIVE: We aimed to examine associations between major n-6 fatty acids [ie, linoleic acid (LA, 18:2n-6) and arachidonic acid (AA, 20:4n-6)] and the lipoprotein subclasses VLDL, LDL, and HDL. DESIGN: We conducted a cross-sectional study in 1098 participants using population-based data from US white, Japanese American, Japanese, and Korean men aged 40-49 y. Serum fatty acids were analyzed by capillary gas-liquid chromatography. Lipoprotein subclasses were measured by nuclear magnetic resonance spectroscopy. Multiple linear regression models as a function of each fatty acid were used after adjustment for age, population, body mass index, pack-years of smoking, alcohol consumption, diabetes, hypertension, and omega-3 (n-3) and trans fatty acids. RESULTS: Serum LA was inversely associated with large VLDL (beta = -0.62, P < 0.001), total LDL (beta = -22.08, P < 0.001), and small LDL (beta = -31.89, P < 0.001) particle concentrations and VLDL size (beta = -0.72, P < 0.001). Serum LA was positively associated with large HDL particle concentration (beta = 0.21, P < 0.001) and HDL size (beta = 0.03, P < 0.001). The patterns of association of AA with large VLDL and large HDL particle concentrations were comparable with those of LA. CONCLUSIONS: At the population level, higher serum concentrations of LA were significantly associated with lower concentrations of total LDL particles. Higher serum concentrations of LA and AA were significantly associated with a lower concentration of large VLDL particles and a higher concentration of large HDL particles. These associations were consistent across the population groups. This trial was registered at clinicaltrials.gov as NCT00069797.

Stronger associations of sagittal abdominal diameter with atherogenic lipoprotein subfractions than waist circumference in middle-aged US white and Japanese men.

Both sagittal abdominal diameter (SAD) and waist circumference (WC) highly correlate with visceral adipose tissue (VAT) being linked to an atherogenic lipoprotein profile. However, it is uncertain whether SAD is a better correlate of atherogenic lipoprotein subfractions than WC. We examined relative associations of SAD vs WC with lipoprotein subfractions for US white and Japanese men, concurrently examining the associations of VAT vs subcutaneous adipose tissue with lipoprotein subfractions. A population-based sample of 260 white and 282 Japanese men aged 40 to 49 years was examined for VAT and subcutaneous adipose tissue by computed tomography; SAD and WC by a portable sliding-beam caliper and a measuring tape, respectively; and lipoprotein subfractions by nuclear magnetic resonance spectroscopy. Both SAD and WC were significantly and positively associated with large very low-density lipoprotein and total and small low-density lipoprotein particle concentrations, and inversely associated with large high-density lipoprotein particle concentration for both white and Japanese men. In body mass index-adjusted regression models, the significant associations of SAD remained for both white and Japanese men, whereas those of WC became nonsignificant for white men. When SAD and WC were simultaneously included into the body mass index-adjusted models, the associations of SAD remained significant and statistically stronger than those of WC for both white and Japanese men. Furthermore, the pattern of the associations of SAD with those lipoprotein subfractions was comparable to that of the associations of VAT. Sagittal abdominal diameter was comparable to VAT and stronger than WC in the associations with atherogenic lipoprotein subfractions for middle-aged, nondiabetic, white and Japanese men.

Association of serum n-6 and n-3 polyunsaturated fatty acids with lipids in 3 populations of middle-aged men.

BACKGROUND: The association of serum polyunsaturated fatty acids (PUFAs) with lipids in different populations is not known. OBJECTIVE: Our aim was to examine the association of serum n-6 (omega-6) or n-3 (omega-3) PUFAs with triglycerides or HDL-cholesterol concentrations in 261 white, 285 Japanese, and 212 Japanese American men aged 40-49 y. DESIGN: We used a population-based cross-sectional study. Of the original sample (n = 926), those taking lipid-lowering medications or who had diabetes (n = 168) were excluded. Serum fatty acids were analyzed by capillary gas-liquid chromatography. Multiple regression models as a function of tertile groups of each PUFA were used. RESULTS: Serum n-6 PUFAs were significantly inversely associated with triglycerides across populations after adjustment for age, body mass index, pack-years of smoking, and ethanol consumption [beta = -0.39 (P < 0.001), -0.38 (P < 0.001), and -0.33 (P < 0.001) in whites, Japanese, and Japanese Americans, respectively]. Marine n-3 PUFAs were significantly inversely associated with triglycerides across populations [beta = -0.15 (P < 0.001), -0.22 (P < 0.001), and -0.13 (P < 0.001) in whites, Japanese, and Japanese Americans, respectively]. n-6 PUFAs were significantly positively associated with HDL cholesterol in whites (beta = 4.49, P < 0.001) and Japanese (beta = 3.73, P < 0.01). Marine n-3 PUFAs were significantly positively associated with HDL cholesterol in Japanese (beta = 2.15, P < 0.05), and eicosapentaenoic acid was significantly positively associated with HDL cholesterol in whites (beta = 2.68, P < 0.01). CONCLUSION: Serum n-6 and n-3 PUFAs are inversely associated with triglycerides across populations.