Tiina H Rissanen

University of Kuopio, Kuopio, Eastern Finland Province, Finland

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Publications (45)210.25 Total impact

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    ABSTRACT: Several previous epidemiological studies have suggested that high plasma concentrations of carotenoids may slow the development of early atherosclerosis, but results have been inconclusive. We examined the effect of carotenoids on early atherosclerosis in a population-based study. The association between plasma carotenoid concentrations and intima-media thickness of the common carotid artery (CCA-IMT) was investigated in 1212 elderly men (aged 61-80 years) in Eastern Finland. They were examined by B-mode ultrasound to detect early signs of carotid atherosclerosis, and plasma concentrations of carotenoids were measured by high-performance liquid chromatography. Men in the lowest quartile of CCA-IMT had significantly higher concentrations of plasma β-cryptoxanthin, lycopene and α-carotene than men in the highest quartile (P for the differences: 0.043, 0.045 and 0.046, respectively), after adjustment for age, examination year, body mass index, smoking, alcohol intake, years of education, symptomatic coronary heart disease (CHD) or CHD history, diabetes, low-density lipoprotein cholesterol, medications and season. The concentrations of plasma β-cryptoxanthin, lycopene and α-carotene decreased linearly with increasing CCA-IMT. The results of this study suggest that high plasma concentrations of β-cryptoxanthin, lycopene and α-carotene may be associated with decreased carotid atherosclerosis in elderly men from eastern Finland.
    Journal of Internal Medicine 05/2011; 270(5):478-85. · 6.46 Impact Factor
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    ABSTRACT: The role of dietary glycemic index (GI) and glycemic load (GL) in coronary heart disease (CHD) is unclear. Our aim was to study the association between the dietary GI and GL and the risk of acute myocardial infarction (AMI). The study population consisted of 1981 Finnish men from the prospective population-based Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study, aged 42-60 years and free of CHD at baseline. During an average follow-up time of 16.1 years, 376 new AMI events occurred. In multivariable-adjusted Cox proportional hazards models, the relative risk (RR) for AMI in the highest quartile of GI was 1.25 (95% CI: 0.92-1.69; P for trend=0.08) and for GL 1.11 (95% CI: 0.79-1.57; P for trend=0.21) when compared with the lowest quartile. For overweight (BMI ≥ 27.5 kg/m²) men, the multivariable-adjusted RR for AMI in the highest compared to the lowest tertile of GI and GL were 1.58 (95% CI: 1.03-2.43; P for trend=0.04, P for interaction=0.01) and 2.05 (95% CI: 1.30-3.23; P for trend=0.002, P for interaction=0.002), respectively. For physically less active men; energy expenditure for leisure-time physical activity < 50 kcal/d, the RR for AMI was 1.72 (95% CI: 1.07-2.76; P for trend=0.04, P for interaction 0.80) with higher GL. Our results suggest that both high dietary GI and GL are associated with increased risk of AMI among overweight and GL possibly among less physically active men.
    Nutrition, metabolism, and cardiovascular diseases: NMCD 10/2009; 21(2):144-9. · 3.52 Impact Factor
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    ABSTRACT: Oxidative modification of low-density lipoprotein (LDL) in the vascular endothelium is considered to be important in the development of early atherosclerosis. The aim of this study was to investigate the main determinants of serum LDL conjugated dienes in women (n=124) and men (n=225). We focused on the influence of fat-soluble vitamins and carotenoids on the concentration of conjugated dienes in LDL. In multivariate linear regression models, including age, body mass index, diastolic blood pressure, symptomatic ischaemic heart disease (IHD) or IHD history, statin medication, leukocytes and serum triglycerides as covariates, plasma lycopene (standardized beta=-0.33; P=0.002) and lutein (standardized beta=-0.22; P=0.027) concentrations were the strongest determinants of serum LDL conjugated dienes in women, whereas plasma beta-carotene (standardized beta=-0.23; P=0.002) was the most important factor in men. Furthermore, statin medication, diastolic blood pressure, age and serum triglycerides were significant determinants of LDL conjugated dienes. The regression model with lycopene contributed to 29% in women and 15% in men with beta-carotene of the variation of serum LDL conjugated dienes. Results of the present study suggest that plasma lycopene, lutein and beta-carotene are the most powerful antioxidants for explaining the content of in vivo oxidatively modified LDL in serum.
    Atherosclerosis 10/2009; 209(2):565-72. · 3.71 Impact Factor
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    ABSTRACT: Lycopene is thought to decrease the risk of cancers, although previous epidemiologic studies have produced inconsistent results. The aim of the present study was to evaluate the protective effect of lycopene against the risk of cancer. The study population consisted of 997 middle-aged Finnish men in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) cohort. During the mean follow-up time of 12.6 years, a total of 141 cancer cases appeared, of which 55 were prostate cancers. The association between the serum concentrations of lycopene and the risk of cancer was studied using the Cox proportional hazard models. An inverse association was observed between serum lycopene and overall cancer incidence. The adjusted risk ratio (RR) in the highest tertile of serum lycopene was 0.55 (95% confidence interval [CI], 0.34-0.89; p=0.015) compared with the lowest serum lycopene group. No association was observed between the lycopene concentrations and a prostate cancer risk. RR for other cancers was 0.43 (95% CI, 0.23-0.79; p=0.007). These findings suggest that in middle-aged men, the higher circulating concentrations of lycopene may contribute to the lower risk of cancer, with the exception of prostate cancer.
    Annals of epidemiology 06/2009; 19(7):512-8. · 2.95 Impact Factor
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    ABSTRACT: To characterize the relation between an exposure and a continuous outcome, the sampling of subjects can be done much as it is in a case-control study, such that the sample is enriched with subjects who are especially informative. In an outcome-dependent sampling design, observations made on a judiciously chosen subset of the base population can provide nearly the same statistical efficiency as observing the entire base population. Reaping the benefits of such sampling, however, requires use of an analysis that accounts for the outcome-dependent sampling. In this report, we examine the statistical efficiency of a plain random sample analyzed with standard methods, compared with that of data collected with outcome-dependent sampling and analyzed by either of 2 appropriate methods. In addition, 3 real datasets were analyzed using an outcome-dependent sampling approach. The results demonstrate the improved statistical efficiency obtained by using an outcome-dependent sampling, and its applicability in a wide range of settings. This design, coupled with an appropriate analysis, offers a cost-efficient approach to studying the determinants of a continuous outcome.
    Epidemiology 08/2007; 18(4):461-8. · 5.74 Impact Factor
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    ABSTRACT: Mercury is a heavy metal that exists naturally in the environment. Major sources include the burning of fossil fuels (especially coal) and municipal waste incineration. Mercury can exist in several forms, with the most hazardous being organic methylmercury. In waterways (lakes, rivers, reservoirs, etc.), mercury is converted to methylmercury, which then accumulates in fish, especially in large predatory fish. Fish and fish products are the major--if not the only--source of methylmercury in humans. Mercury has long been recognized as a neurotoxin for humans, but in the last 10 years, its potentially harmful effects on cardiovascular diseases (CVD) have raised a cause for concern, mostly due to the proposed role of mercury in oxidative stress propagation. Some epidemiological studies have indeed found an association between increased levels of mercury in the body and risk of CVD. There are several plausible mechanisms to explain the association; these are discussed in this review. We also review the epidemiological studies that have investigated the association between mercury and CVD.
    The Journal of Nutritional Biochemistry 03/2007; 18(2):75-85. · 4.55 Impact Factor
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    ABSTRACT: Astaxanthin, the main carotenoid pigment in aquatic animals, has greater antioxidant activity in vitro (protecting against lipid peroxidation) and a more polar configuration than other carotenoids. We investigated the effect of three-month astaxanthin supplementation on lipid peroxidation in healthy non-smoking Finnish men, aged 19-33 years by using a randomized double-blind study design. Also absorption of astaxanthin from capsules into bloodstream and its safety were evaluated. The intervention group received two 4-mg astaxanthin (Astaxin) capsules daily, and the control group two identical-looking placebo capsules. Astaxanthin supplementation elevated plasma astaxanthin levels to 0.032 pmol/L (p < 0.001 for the change compared with the placebo group). We observed that levels of plasma 12- and 15-hydroxy fatty acids were reduced statistically significantly in the astaxanthin group (p = 0.048 and p = 0.047 respectively) during supplementation, but not in the placebo group and the change of 15-hydroxy fatty acid was almost significantly greater (p = 0.056) in the astaxanthin group, as compared with the placebo group. The present study suggests that intestinal absorption of astaxanthin delivered as capsules is adequate, and well tolerated. Supplementation with astaxanthin may decrease in vivo oxidation of fatty acids in healthy men.
    International Journal for Vitamin and Nutrition Research 01/2007; 77(1):3-11. · 1.27 Impact Factor
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    ABSTRACT: Cardiovascular disease (CVD) is the main cause of death in Western countries. Nutrition has a significant role in the prevention of many chronic diseases such as CVD, cancers, and degenerative brain diseases. The major risk and protective factors in the diet are well recognized, but interesting new candidates continue to appear. It is well known that a greater intake of fruit and vegetables can help prevent heart diseases and mortality. Because fruit, berries, and vegetables are chemically complex foods, it is difficult to pinpoint any single nutrient that contributes the most to the cardioprotective effects. Several potential components that are found in fruit, berries, and vegetables are probably involved in the protective effects against CVD. Potential beneficial substances include antioxidant vitamins, folate, fiber, and potassium. Antioxidant compounds found in fruit and vegetables, such as vitamin C, carotenoids, and flavonoids, may influence the risk of CVD by preventing the oxidation of cholesterol in arteries. In this review, the role of main dietary carotenoids, ie, lycopene, beta-carotene, alpha-carotene, beta-cryptoxanthin, lutein, and zeaxanthin, in the prevention of heart diseases is discussed. Although it is clear that a higher intake of fruit and vegetables can help prevent the morbidity and mortality associated with heart diseases, more information is needed to ascertain the association between the intake of single nutrients, such as carotenoids, and the risk of CVD. Currently, the consumption of carotenoids in pharmaceutical forms for the treatment or prevention of heart diseases cannot be recommended.
    American Journal of Clinical Nutrition 07/2006; 83(6):1265-71. · 6.50 Impact Factor
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    ABSTRACT: Homocysteine, a methionine metabolite, is suggested to be a risk factor for cardiovascular diseases (CVD). To date, the effects of dietary intake of methionine, the key amino acid in homocysteine metabolism, on CVD have not been studied. Our aim was to examine the effects of dietary methionine intake on the risk of acute coronary events. We examined the effects of dietary methionine intake, assessed with 4-d food record, on acute coronary events in a prospective cohort study consisting of 1981 coronary disease free men from eastern Finland, aged 42-60 years at baseline in 1984-89, in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. During an average follow-up time of 14.0 years, 292 subjects experienced an acute coronary event. In a Cox proportional hazards model adjusting for age, examination years, BMI, urinary nicotine metabolites and protein intake (excluding methionine) the relative risks of acute coronary event in the three highest quarters of dietary methionine intake were 1.31 (95% CI: 0.92, 1.86), 1.31 (95% CI: 0.88, 1.96) and 2.08 (95% CI: 1.31, 3.29) as compared with the lowest quarter. Further adjustments did not change the results. However, opposite association was observed with total protein intake, which tended to decrease the risk. The main finding of this study is that long-term, moderately high dietary methionine intake may increase the risk of acute coronary events in middle-aged Finnish men free of prior CHD. More prospective research is needed to confirm the role of dietary methionine in the development of CVD, and whether its effects are independent of homocysteine.
    Nutrition Metabolism and Cardiovascular Diseases 04/2006; 16(2):113-20. · 3.98 Impact Factor
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    ABSTRACT: Homocysteine and folate have been suggested to have opposite effects on the risk of stroke, although the results are controversial. The purpose of this study was to assess the effects of serum total homocysteine (tHcy) and serum folate levels on the risk of stroke in a prospective cohort study. The subjects were 1015 men aged 46-64 years and free of prior stroke, examined in 1991-1993 in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. At baseline the mean serum tHcy concentration was 10.9 micromol/l (SD 3.4). During an average follow-up time of 9.6 years, 49 men experienced a stroke, of which 34 were ischaemic. In Cox proportional hazards models, men in the highest tHcy third had a risk factor-adjusted hazard rate ratio (RR) of 2.77 [95% confidence interval (CI): 1.23-6.24] for any stroke and 2.61 (95% CI: 1.02-6.71) for ischaemic stroke, compared with men in the lowest third. The mean baseline serum folate concentration was 10.4 nmol/l (SD 4.1). Men in the highest third of serum folate (>11.2 nmol/l) had an adjusted RR for any stroke of 0.35 (95% CI: 0.14-0.87) and for ischaemic stroke of 0.40 (95% CI: 0.15-1.09), compared with men in the lowest third. Elevated serum tHcy is associated with increased risk of all strokes and ischaemic strokes in middle-aged eastern Finnish men free of prior stroke. On the other hand, high serum folate concentration may protect against stroke.
    European Journal of Cardiovascular Prevention and Rehabilitation 09/2005; 12(4):369-75. · 2.63 Impact Factor
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    ABSTRACT: In humans, polyphenol supplementation studies have resulted in inconsistent findings in lipid peroxidation. Our aim was to investigate the effects of a 4-week consumption of polyphenol-rich phloem on serum lipids and lipid peroxidation in the hydrophilic fraction of serum and on isolated lipoproteins. We conducted a randomized double-blind supplementation study consisting of 75 nonsmoking hypercholesterolemic men. Participants consumed 70 g daily of either rye bread (placebo) or phloem-fortified rye bread containing 31 mg (low polyphenol, LP) or 62 mg (high polyphenol, HP) of catechins. The ex vivo susceptibility of total serum lipids and VLDL and LDL to oxidation after copper induction was measured as a lag time to the maximal oxidation rate at the baseline and after the supplementation. In the HP group, an increase in the oxidation resistance of total serum lipids was observed (11.4%), while no effect was seen in the LP group (-0.8%) or in the placebo group (-1.0%) (p = 0.007). No differences were observed in the oxidation resistance of VLDL and LDL between the study groups. The phloem also increased in vitro oxidation resistance of serum lipids and radical scavenging activity (DPPH.) in a dose-dependent manner. Our results suggest that polyphenols may inhibit lipid peroxidation in the hydrophilic fraction of serum.
    Journal of Agricultural and Food Chemistry 05/2005; 53(8):3017-22. · 2.91 Impact Factor
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    ABSTRACT: Based on case-control and prospective studies elevated blood total homocysteine (tHcy) has been suggested to be an independent risk factor for cardiovascular diseases (CVD). The purpose of the study was to explore the joint effect of increased serum tHcy concentration and other risk factors on the risk of CVD mortality in middle-aged men without a history of heart disease or stroke. A prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. Eastern Finland. Subjects. A total of 802 men aged 46-64 years, examined in 1991-93. CVD mortality event. The mean serum tHcy concentration was 10.8 micromol L(-1) (SD 3.3). During the average follow-up time of 10.8 years 50 men experienced a CVD death. The hazard rate ratio for CVD mortality was 1.80 (95% confidence interval: 1.02-3.19) in men in the highest serum tHcy third versus lower thirds after adjustment for cardiovascular risk factors. Furthermore, elevated serum tHcy concentration appeared to increase the risk of CVD death in men who smoke or who have high circulating concentrations of serum total or LDL cholesterol, apo-B apolipoprotein or plasma fibrinogen. We conclude that homocysteine may increase the risk of CVD mortality in middle-aged men from Eastern Finland, and it may especially increase the risk when present with other risk factors for CVD.
    Journal of Internal Medicine 04/2005; 257(3):255-62. · 6.46 Impact Factor
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    ABSTRACT: Despite extensive research, the cardiovascular effects of coffee consumption in humans remain controversial. Our aim was to investigate the excretion of coffee phenols and the effects of filtered coffee consumption on oxidative stress and plasma homocysteine (tHcy) concentration in humans. The study consisted of a multiple-dose clinical supplementation trial and a single-dose study. In the long-term trial, 43 healthy nonsmoking men optionally consumed daily either no coffee, 3 cups (450 mL), or 6 cups (900 mL) of filtered coffee for 3 weeks, while in the short-term study 35 subjects consumed a single dose of 0, 1 (150 mL), or 2 cups (300 mL) of coffee. Long-term consumption of coffee increased the urinary excretion of caffeic and ferulic acid. The change in the total excretion of phenolic acids in 3 and 6 cups groups represented 3.8 and 2.5% of the amount ingested daily. Plasma tHcy concentrations increased nonsignificantly, but the consumption of coffee had neither short-nor long-term effects on lipid peroxidation or the activity of measured antioxidant enzymes. In conclusion, the consumption of filtered coffee does not have any detectable effects on lipid peroxidation in healthy nonsmoking men. The effect of coffee consumption on tHcy concentrations needs further investigation.
    Free Radical Biology and Medicine 03/2005; 38(4):527-34. · 5.27 Impact Factor
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    ABSTRACT: Substitution of dietary polyunsaturated for saturated fat has long been recommended for the primary prevention of cardiovascular disease (CVD), but only a few prospective cohort studies have provided support for this advice. We assessed the association of dietary linoleic and total polyunsaturated fatty acid (PUFA) intake with cardiovascular and overall mortality in a population-based cohort of 1551 middle-aged men. Dietary fat composition was estimated with a 4-day food record and serum fatty acid composition. During the 15-year follow-up, 78 men died of CVD and 225 of any cause. Total fat intake was not related to CVD or overall mortality. Men with an energy-adjusted dietary intake of linoleic acid (relative risk [RR] 0.39; 95% confidence interval [CI], 0.21-0.71) and PUFA (RR, 0.38; 95% CI, 0.20-0.70) in the upper third were less likely to die of CVD than men with intake in the lower third after adjustment for age. Multivariate adjustment weakened the association somewhat. Mortality from CVD was also lower for men with proportions of serum esterified linoleic acid (RR, 0.42; 95% CI, 0.21-0.80) and PUFA (RR, 0.25; 95% CI, 0.12-0.50) in the upper vs lower third, with some attenuation in multivariate analyses. Serum and to a lesser extent dietary linoleic acid and PUFA were also inversely associated with overall mortality. Dietary polyunsaturated and more specifically linoleic fatty acid intake may have a substantial cardioprotective benefit that is also reflected in overall mortality. Dietary fat quality seems more important than fat quantity in the reduction of cardiovascular mortality in men.
    Archives of Internal Medicine 02/2005; 165(2):193-9. · 11.46 Impact Factor
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    ABSTRACT: http://deepblue.lib.umich.edu/bitstream/2027.42/51491/1/Virtanen JK, Homocysteine as a Risk Factor for CVD, 2005.pdf
    Journal of Internal Medicine 01/2005; · 6.46 Impact Factor
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    ABSTRACT: Mercury has been suggested to have negative effects on cardiovascular health. We investigated the effects of high mercury content in hair on the risk of acute coronary events and cardiovascular and all-cause mortality in men from eastern Finland. The population-based prospective Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) cohort of 1871 Finnish men aged 42 to 60 years and free of previous coronary heart disease (CHD) or stroke at baseline was used. During an average follow-up time of 13.9 years, 282 acute coronary events and 132 cardiovascular disease (CVD), 91 CHD, and 525 all-cause deaths occurred. Men in the highest third of hair mercury content (>2.03 microg/g) had an adjusted 1.60-fold (95% CI, 1.24 to 2.06) risk of acute coronary event, 1.68-fold (95% CI, 1.15 to 2.44) risk of CVD, 1.56-fold (95% CI, 0.99 to 2.46) risk of CHD, and 1.38-fold (95% CI, 1.15 to 1.66) risk of any death compared with men in the lower two thirds. High mercury content in hair also attenuated the protective effects of high-serum docosahexaenoic acid plus docosapentaenoic acid concentration. High content of mercury in hair may be a risk factor for acute coronary events and CVD, CHD, and all-cause mortality in middle-aged eastern Finnish men. Mercury may also attenuate the protective effects of fish on cardiovascular health.
    Arteriosclerosis Thrombosis and Vascular Biology 01/2005; 25(1):228-33. · 6.34 Impact Factor
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    ABSTRACT: Cocoa powder is rich in polyphenols and, thus, may contribute to the reduction of lipid peroxidation. Our aim was to study the effects of long-term ingestion of chocolate, with differing amounts of polyphenols, on serum lipids and lipid peroxidation ex vivo and in vivo. We conducted a 3 week clinical supplementation trial of 45 nonsmoking, healthy volunteers. Participants consumed 75 g daily of either white chocolate (white chocolate, WC group), dark chocolate (dark chocolate, DC group), or dark chocolate enriched with cocoa polyphenols (high-polyphenol chocolate, HPC group). In the DC and HPC groups, an increase in serum HDL cholesterol was observed (11.4% and 13.7%, respectively), whereas in the WC group there was a small decrease (-2.9%, p < 0.001). The concentration of serum LDL diene conjugates, a marker of lipid peroxidation in vivo, decreased 11.9% in all three study groups. No changes were seen in the total antioxidant capacity of plasma, in the oxidation susceptibility of serum lipids or VLDL + LDL, or in the concentration of plasma F2-isoprostanes or hydroxy fatty acids. Cocoa polyphenols may increase the concentration of HDL cholesterol, whereas chocolate fatty acids may modify the fatty acid composition of LDL and make it more resistant to oxidative damage.
    Free Radical Biology and Medicine 11/2004; 37(9):1351-9. · 5.27 Impact Factor
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    ABSTRACT: Dietary and serum fatty acid composition has been implicated in the pathogenesis of prostate and other cancers, but findings have been conflicting. Cohort studies reporting serum fatty acid composition are lacking. We assessed the association of fatty acid composition determined from dietary records and serum with incident cancer of the prostate and any site in a population-based cohort of 2,002 middle-aged Finnish men who were free of cancer at baseline and during the first 4 years of follow-up. During 12.6 years of follow-up, 46 men developed prostate cancer and 151 any cancer. Men with proportions of serum nonesterified [risk ratio (RR) 0.28; 95% confidence intervals (CI) 0.12-0.66] and esterified linoleic acid (RR 0.37; 95% CI = 0.16-0.86) and total polyunsaturated fatty acids (RR 0.30; 95% CI = 0.12-0.71) in the upper third were less than 1/3 as likely to develop prostate cancer during follow-up. Adjustment for possible confounders like socioeconomic status, physical activity, obesity and insulin concentrations did not attenuate the association. Similar but weaker associations with any cancer were found. Dietary linoleic acid intake also tended to be inversely associated with incident prostate cancer (age-adjusted RR for the upper vs. lower third 0.55; 95% CI = 0.26-1.14, p for the trend 0.097). Substitution of linoleic acid for saturated fat in middle-aged men consuming a high saturated-fat diet may decrease the risk of prostate and other cancers, although it is possible that some of the effect may be mediated by nutrients closely associated with vegetable fats.
    International Journal of Cancer 10/2004; 111(3):444-50. · 6.20 Impact Factor
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    ABSTRACT: Several, but not all, prospective studies have shown that low folate intakes, low circulating folate concentrations, or high plasma total homocysteine (tHcy) concentrations are associated with an increased risk of coronary artery disease (CAD). We examined the relations of both serum folate and serum tHcy concentrations with acute coronary events in middle-aged men from eastern Finland who had no CAD at baseline. In a population-based prospective cohort study, 1027 men aged 46-64 y were examined in 1991-1993 as part of the Kuopio Ischaemic Heart Disease Risk Factor Study. During an average follow-up of 7.7 y (7900 person-years of follow-up), 114 acute coronary events were observed in 61 men who had no previous history of CAD (n = 810). In a Cox model, compared with men whose serum folate concentrations were in the lowest tertile, those whose concentrations were in the highest tertile had a risk factor-adjusted relative risk of acute coronary events of 0.35 (95% CI: 0.17, 0.73; P = 0.005). Serum tHcy concentrations were not significantly associated with the risk of acute coronary events (for the highest tertile compared with the lowest, adjusted relative risk = 1.03; 95% CI: 0.57, 1.87; P = 0.932). The results of this prospective cohort study do not support the hypothesis that a high circulating tHcy concentration is a risk factor for acute coronary events in a male population free of prior heart disease. However, they do suggest that moderate-to-high serum folate concentrations are associated with a greatly reduced incidence of acute coronary events.
    American Journal of Clinical Nutrition 09/2004; 80(2):317-23. · 6.50 Impact Factor
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    ABSTRACT: http://deepblue.lib.umich.edu/bitstream/2027.42/51488/1/Voutilainen S, Serum Folate and Homocysteine, 2004.pdf
    01/2004;