Markers associated with genomic instability, immunogenicity and immune therapy responsiveness in Metaplastic carcinoma of the breast: Expression of γH2AX, pRPA2, P53, PD-L1 and tumor infiltrating lymphocytes in 76 cases.

BACKGROUND: Metaplastic breast cancer (MpBC) is an aggressive subtype of breast carcinoma that is often resistant to conventional chemotherapy. Therefore, novel treatment strategies are urgently needed. Immune check point inhibitors have shown activity in programmed death-ligand 1 (PD-L1) - positive metastatic triple negative breast carcinoma (TNBC), which raises the possibility that immunotherapy may also be effective in MpBC as most of the MpBCs are triple negative. The aim of the present study was to assess genomic instability and immunogenicity in tumor specimens of patients with MpBC. METHODS: A total of 76 patients diagnosed with MpBC over a 15-year period were included in the study. We performed immunohistochemical analyses for tumor cell PD-L1, immune cell PD-L1 and p53 on tissue microarrays (TMAs), analyzed stromal and intratumoral tumor infiltrating lymphocytes (TILs) from hematoxylin and eosin-stained (H&E) slides and scored gamma-H2AX (γH2AX) and phosphorylated-RPA2 (pRPA2) from whole tissue sections. We correlated marker expression with clinicopathologic features and clinical outcome. RESULTS: All tumors expressed γH2AX and pRPA2 with median expressions of 43% and 44%. P53- (68%), tumor cell PD-L1- (59%) and immune cell PD-L1-positivity (62%) were common in MpBCs. Median stromal TIL and intratumoral TIL counts were 5% and 0. The spindle and squamous cell carcinomas expressed the highest levels of PD-L1 and TILs, and carcinoma with mesenchymal differentiation the lowest. CONCLUSIONS: MpBC appears to be an immunogenic cancer with high genomic instability and frequent PD-L1-positivity, implying that check point inhibitors might be effective in MpBC. Expression levels of PD-L1 and TILs varied across different histologic subtypes, suggesting that immunotherapy might be less effective in carcinoma with mesenchymal differentiation.

Serum Concentrations of 25-Hydroxyvitamin D and Depression in a General Middle-Aged to Elderly Population in Finland.

OBJECTIVES: Low concentrations of serum 25-hydroxyvitamin D [25(OH)D] have been postulated to associate with an increased prevalence of depression. As there are a limited number of publications on this issue, we examined the association between serum 25(OH)D and depression in a general middle-aged or older population. DESIGN: A population-based cross-sectional study. SETTING AND PARTICIPANTS: A total of 1602 men and women from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) in Eastern Finland, aged 53-73 y in 1998-2001, were analysed. MEASUREMENTS: Depressive symptoms were assessed with the DSM-III depression scale, and those individuals who had scores over 4 (range 0-12) or had reported undergoing current antidepressant therapy, were considered as suffering from depression. Associations were estimated in serum 25(OH)D tertiles using logistic regression. RESULTS: Among the participants, 183 subjects (11.4%) were considered to have depression. The mean age of the subjects was 62.6 years (SD 6.4, range 53.4-73.8 years). The mean serum 25(OH)D concentration was 43.8 nmol/L (SD 17.7, range 8.5-112.8 nmol/L), concentrations <50 nmol/L were observed in 65.0% of the subjects, and only 5.0% displayed concentrations ≥75 nmol/L. After multivariable adjustments, the odds ratios for having depression in the tertiles (from highest to the lowest) of serum 25(OH)D were 1, 1.35 (95 % CI: 0.87, 2.09) and 1.64 (95 % CI: 1.03, 2.59), P for trend=0.036. CONCLUSION: These findings indicate that a lower concentration of serum 25(OH)D is associated with a higher prevalence of depression in an elderly general population.

Omega-6 polyunsaturated fatty acids, serum zinc, delta-5- and delta-6-desaturase activities and incident metabolic syndrome.

BACKGROUND: The associations of n-6 polyunsaturated fatty acids (PUFA) with metabolic syndrome have been poorly explored. We investigated the associations of the serum n-6 PUFA and the activities of enzymes involved in the PUFA metabolism, delta-5-desaturase (D5D) and delta-6-desaturase (D6D) with risk of incident metabolic syndrome. We also investigated whether zinc, a cofactor for these enzymes, modifies these associations. METHODS: A prospective follow-up study was conducted on 661 men who were aged 42-60 years old at baseline in 1984-1989 and who were re-examined in 1998-2001. RESULTS: Men in the highest versus the lowest serum total omega-6 PUFA tertile had a 70% lower multivariate-adjusted risk of incident metabolic syndrome [odds ratio (OR) = 0.30; 95% confidence interval (CI) = 0.18-0.51, Ptrend < 0.001]. Inverse associations were also observed for linoleic acid, arachidonic acid and D5D activity. By contrast, men in the highest tertile of D6D activity had an 84% higher risk (OR = 1.84; 95% CI = 1.15-2.94, Ptrend = 0.008). Similar associations were observed with many of the metabolic syndrome components at the re-examinations. Most associations were attenuated after adjustment for body mass index. Finally, the associations of D6D and LA were stronger among those with a higher serum zinc concentration. CONCLUSIONS: Higher serum total n-6 PUFA, linoleic acid and arachidonic acid concentrations and D5D activity were associated with a lower risk of developing metabolic syndrome and higher D6D activity was associated with a higher risk. The role of zinc also needs to be investigated in other populations.

Association between serum long-chain omega-3 polyunsaturated fatty acids and cognitive performance in elderly men and women: The Kuopio Ischaemic Heart Disease Risk Factor Study.

BACKGROUND/OBJECTIVES: Fish intake and the long-chain omega-3 polyunsaturated fatty acids (PUFAs) in fish have been suggested to lower the risk of cognitive decline. We assessed whether serum long-chain omega-3 PUFAs eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) are associated with performance on neuropsychological tests in an older population and whether exposure to methylmercury, mainly from fish, or apolipoprotein-E4 (Apo-E4) phenotype can modify the associations. SUBJECTS/METHODS: A total of 768 participants from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study were included. Cognitive function was measured using five neuropsychological tests: the Trail Making Test, the Verbal Fluency Test, the Selective Reminding Test, the Visual Reproduction Test and the Mini Mental State Exam. Multivariate-adjusted analysis of covariance and linear regression were used to analyze the cross-sectional associations. RESULTS: We found statistically significant associations between serum EPA+DPA+DHA and better performance in the Trail Making Test and the Verbal Fluency Test. The individual associations with EPA and DHA were similar with the findings with EPA+DPA+DHA, although the associations with DHA were stronger. No associations were observed with serum DPA. Pubic hair mercury content was associated only with a worse performance in the Trail Making Test, and mercury had only little impact on the associations between the serum PUFAs and cognitive performance. Apo-E4 phenotype did not modify the associations with PUFAs or mercury. CONCLUSIONS: Higher serum long-chain omega-3 PUFA concentrations were associated with better performance on neuropsychological tests of frontal lobe functioning in older men and women. Mercury exposure or Apo-E4 phenotype had little impact on cognitive performance.

Serum long-chain omega-3 polyunsaturated Fatty acids and future blood pressure in an ageing population.

OBJECTIVES: To investigate the associations of serum long-chain omega-3 polyunsaturated fatty acids (PUFA) and hair mercury with future blood pressure in an ageing population. DESIGN: Prospective study with baseline measurements in 1998-2001 and follow-up measurements in 2005-2008. The linear relationships (ß) of baseline serum fatty acids and hair mercury with future systolic and diastolic blood pressure and pulse pressure were analyzed with multiple linear regression models, using log-transformed values. PARTICIPANTS: 181 men and 200 women aged 53-73 y from the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD) population in Eastern Finland, who were free of cardiovascular disease, diabetes or hypertension at baseline. MEASUREMENTS: Total serum esterified and nonesterified fatty acids and pubic hair mercury were used as markers for exposure. Anthropometric and other lifestyle and health-related data were collected. RESULTS: The mean serum concentrations were 1.67% (SD 0.92) for eicosapentaenoic acid (EPA), 0.79% (SD 0.16) for docosapentaenoic acid (DPA) and 2.78 (SD 0.92) for docosahexaenoic acid (DHA), of all serum fatty acids. The mean hair mercury concentration was 1.5 µg/g (SD 1.6). We did not find statistically significant associations between the baseline serum long-chain omega-3 PUFA concentrations or hair mercury content and future blood pressure. Hair mercury did not modify the associations with the long-chain omega-3 PUFAs, either. CONCLUSIONS: Higher serum long-chain omega-3 PUFA concentration, a biomarker of fish or fish oil consumption, may not have an impact on future blood pressure in an ageing population.

How does lifestyle intervention affect depressive symptoms? Results from the Finnish Diabetes Prevention Study.

AIMS: To assess the effect of lifestyle intervention on depressive symptoms during a 36-month randomized clinical trial designed to prevent Type 2 diabetes. METHODS: A total of 522 middle-aged participants, who were overweight or obese and had impaired glucose tolerance, were randomized to the lifestyle intervention or control group in the Finnish Diabetes Prevention Study. The intervention group received individualized counselling aimed at reducing weight and increasing physical activity. Depressive symptoms were measured using the Beck Depression Inventory among a subgroup of 140 participants. RESULTS: On study entry, the mean Beck Depression Inventory scores ± sd were 6.8 ± 5.6 in the intervention group and 6.7 ± 5.5 in the control group. Beck Depression Inventory scores reduced during the intervention study: the mean ± sd (95% CI) reduction was 0.90 ± 4.54 (-1.99 to -0.19) scores in the intervention group and 0.75 ± 4.47 (-1.80 to 0.31) in the control group, with no difference between the groups. In a stepwise linear multivariate regression analysis, the variables with the strongest associations with the change in Beck Depression Inventory scores were baseline Beck Depression Inventory scores, marital status, weight change and change of total energy intake (R(2) = 0.209, P < 0.001). CONCLUSIONS: Participation in the study lowered depression scores, with no specific group effect. Among the lifestyle changes, particularly successful reduction of body weight was associated with the greater reduction of depressive symptoms. Thus, regardless of the intensity of the treatment, the success in executing alterations in one's lifestyle and behaviour is associated with beneficial changes in mood.

Glycemic index, glycemic load, and the risk of acute myocardial infarction in Finnish men: the Kuopio Ischaemic Heart Disease Risk Factor Study.

BACKGROUND AND AIM: 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). METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Homocysteine as a risk factor for CVD mortality in men with other CVD risk factors: the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study.

OBJECTIVE: 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. DESIGN: A prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. SETTING: Eastern Finland. Subjects. A total of 802 men aged 46-64 years, examined in 1991-93. MAIN OUTCOME MEASURES: CVD mortality event. RESULTS: 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. CONCLUSION: 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.

Phloem fortification in rye bread elevates serum enterolactone level.

OBJECTIVE: To analyse the lignan content of phloem powder enriched rye bread and to study the dose-response relationship of the effect of dietary plant lignans derived from phloem on intestinal production of enterolactone by measuring enterolactone concentration in serum. DESIGN: A randomized double-blind supplementation trial. SUBJECTS: Seventy-five non-smoking men recruited by newspaper advertisements. INTERVENTION: Subjects were randomized to three study groups receiving either rye bread high in phloem (HP, 14% of rye flour substituted with phloem powder), rye bread low in phloem (LP, 7% of rye flour substituted with phloem powder) or placebo rye bread. Participants consumed 70 g of study bread daily for 4 weeks and provided serum samples for enterolactone analysis at baseline and at the end of the intervention. RESULTS: There was a significant increase in serum enterolactone concentration in the LP and HP groups compared with the placebo group (P=0.009 and P=0.003, respectively). Considerable interindividual differences were observed in the response to dietary lignans within the study groups. CONCLUSIONS: Our results indicate that plant lignans attached to insoluble fibre layer in phloem can be further metabolized and converted to enterolactone presumably by the bacteria present in the colon. Phloem powder is useful source of lignans for functional foods aimed to elevate serum enterolactone levels. SPONSORSHIP: Phloem powder and the study breads were provided by Finnpettu Oy and Linkosuo Oy, respectively. The clinical study work was sponsored in part by Oy Jurilab Ltd.

Low dietary folate intake is associated with an excess incidence of acute coronary events: The Kuopio Ischemic Heart Disease Risk Factor Study.

BACKGROUND: Although several prospective studies have shown that low folate intake and low circulating folate are associated with increased risk of coronary heart disease (CHD), the findings are inconsistent. METHODS AND RESULTS: We studied the associations of dietary intake of folate, vitamin B(6), and vitamin B(12) with the risk of acute coronary events in a prospective cohort study of 1980 Finnish men 42 to 60 years old examined in 1984 to 1989 in the Kuopio Ischemic Heart Disease Risk Factor Study. Nutrient intakes were assessed by 4-day food record. During an average follow-up time of 10 years, 199 acute coronary events occurred. In a Cox proportional hazards model adjusted for 21 conventional and nutritional CHD risk factors, men in the highest fifth of folate intake had a relative risk of acute coronary events of 0.45 (95% CI 0.25 to 0.81, P=0.008) compared with men in the lowest fifth. This association was stronger in nonsmokers and light alcohol users than in smokers and alcohol users. A high dietary intake of vitamin B(6) had no significant association and that of vitamin B(12) a weak association with a reduced risk of acute coronary events. CONCLUSIONS: The present work in CHD-free middle-aged men is the first prospective cohort study to observe a significant inverse association between quantitatively assessed moderate-to-high folate intakes and incidence of acute coronary events in men. Our findings provide further support in favor of a role of folate in the promotion of good cardiovascular health.

Low serum lycopene concentration is associated with an excess incidence of acute coronary events and stroke: the Kuopio Ischaemic Heart Disease Risk Factor Study.

A number of epidemiological studies have shown an association between beta-carotene and the risk of cardiovascular diseases, whereas only a few studies are available concerning the association of lycopene with the risk of coronary events, and no studies have been undertaken concerning lycopene and stroke. Thus, we tested the hypothesis that low serum levels of lycopene are associated with increased risk of acute coronary events and stroke in middle-aged men previously free of CHD and stroke. The subjects were 725 men aged 46-64 years examined in 1991-3 in the Kuopio Ischaemic Heart Disease Risk Factor Study. Forty-one men had either a fatal or a non-fatal acute coronary event or a stroke by December 1997. In a Cox' proportional hazard's model adjusting for examination years, age, systolic blood pressure and three nutritional factors (serum folate, beta-carotene and plasma vitamin C), men in the lowest quarter of serum lycopene levels (< or =0.07 micromol/l) had a 3.3-fold (95 % CI 1.7, 6.4, risk of acute coronary events or stroke compared with the others. Our study suggests that a low serum level of lycopene is associated with an increased risk of atherosclerotic vascular events in middle-aged men previously free of CHD and stroke.

Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study: a randomized trial of the effect of vitamins E and C on 3-year progression of carotid atherosclerosis.

OBJECTIVES: To study the efficacy of vitamin E and C supplementation on the progression of carotid atherosclerosis, hypothesizing an enhanced preventive effect in men and in smokers and synergism between vitamins. DESIGN AND SUBJECTS: Double-masked two-by-two factorial trial, randomization in four strata (by gender and smoking status) to receive twice daily either 91 mg (136 IU) of d-alpha-tocopherol, 250 mg of slow-release vitamin C, a combination of these or placebo for three years. A randomized sample of 520 smoking and nonsmoking men and postmenopausal women aged 45-69 years with serum cholesterol >/= 5.0 mmol L-1 were studied. SETTING: The population of the city of Kuopio in Eastern Finland. INTERVENTION: Twice daily either a special formulation of 91 mg of d-alpha-tocopherol, 250 mg of slow-release vitamin C, a combination of these (CellaVie(R)) or placebo for three years. MEASUREMENTS: Atherosclerotic progression, defined as the linear regression slope of ultrasonographically assessed common carotid artery mean intima-media thickness (IMT), was calculated over semi-annual assessments. RESULTS: The average increase of the mean IMT was 0.020 mm year-1 amongst men randomized to placebo and 0.018 mm year-1 in vitamin E, 0.017 mm year-1 in vitamin C and 0.011 mm year-1 in the vitamin combination group (P = 0.008 for E + C vs. placebo). The respective means in women were 0.016, 0.015, 0.017 and 0.016 mm year-1. The proportion of men with progression was reduced by 74% (95% CI 36-89%, P = 0.003) by supplementation with the formulation containing both vitamins, as compared with placebo. CONCLUSIONS: Our study shows that a combined supplementation with reasonable doses of both vitamin E and slow-release vitamin C can retard the progression of common carotid atherosclerosis in men. This may imply benefits with regard to other atherosclerosis-based events.

Low plasma lycopene concentration is associated with increased intima-media thickness of the carotid artery wall.

Although a number of epidemiological studies have evaluated the association between ss-carotene and the risk of cardiovascular diseases, there has been little research on the role of lycopene, an acyclic form of ss-carotene, with regard to the risk of cardiovascular disease. We investigated the relationship between plasma concentrations of lycopene and intima-media thickness of the common carotid artery wall (CCA-IMT) in 520 middle-aged men and women (aged 45 to 69 years) in eastern Finland. They were examined from 1994 to 1995 at the baseline of the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study, a randomized trial concerning the effect of vitamin E and C supplementation on atherosclerotic progression. The subjects were classified into 2 categories according to the median concentration of plasma lycopene (0.12 micromol/L in men and 0.15 micromol/L in women). Mean CCA-IMT of the right and left common carotid arteries was 1.18 mm in men and 0.95 mm in women with plasma lycopene levels lower than the median and 0.97 mm in men (P:<0.001 for difference) and 0.89 mm in women (P:=0.027 for difference) with higher levels of plasma lycopene. In ANCOVA adjusting for cardiovascular risk factors and intake of nutrients, in men, low levels of plasma lycopene were associated with a 17.8% increment in CCA-IMT (P:=0.003 for difference). In women, the difference did not remain significant after the adjustments. We conclude that low plasma lycopene concentrations are associated with early atherosclerosis, manifested as increased CCA-IMT, in middle-aged men living in eastern Finland.

Fish oil-derived fatty acids, docosahexaenoic acid and docosapentaenoic acid, and the risk of acute coronary events: the Kuopio ischaemic heart disease risk factor study.

BACKGROUND: Previous findings concerning the serum levels of fish-derived (n-3) fatty acids and coronary heart disease are inconsistent. The purpose of this study was to investigate the association between the serum n-3 end-product fatty acids docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and eicosapentaenoic acid and the risk of acute coronary events in middle-aged men. METHODS AND RESULTS: We studied this association in the Kuopio Ischaemic Heart Disease Risk Factor Study, a prospective population study in Eastern Finland. Subjects were randomly selected and included 1871 men aged 42 to 60 years who had no clinical coronary heart disease at baseline examination. A total of 194 men had a fatal or nonfatal acute coronary event during follow-up. In a Cox proportional hazards' model adjusting for other risk factors, men in the highest fifth of the proportion of serum DHA+DPA in all fatty acids had a 44% reduced risk (P=0.014) of acute coronary events compared with men in the lowest fifth. Men in the highest fifth of DHA+DPA who had a low hair content of mercury (2.0 microgram/g). There was no association between proportion of eicosapentaenoic acid and the risk of acute coronary events. CONCLUSIONS: Our data provide further confirmation for the concept that fish oil-derived fatty acids reduce the risk of acute coronary events. However, a high mercury content in fish could attenuate this protective effect.

Plasma total homocysteine concentration and the risk of acute coronary events: the Kuopio Ischaemic Heart Disease Risk Factor Study.

OBJECTIVES: Results from prospective studies concerning the association between plasma total homocysteine (tHcy) concentration and coronary heart disease (CHD) are conflicting. The purpose of this study was to test the hypothesis that plasma tHcy is associated with an increased risk of acute coronary events in middle-aged men. DESIGN AND SUBJECTS: We investigated this association in a prospective nested case-control study among Eastern Finnish men aged 42-60 years. Plasma tHcy measurements were carried out for 163 men who had an acute coronary event during an average 8 years and 11 months follow-up of the whole cohort and for 163 control subjects. Both the cases and the controls were from a cohort of 2005 men who had no clinical CHD at the Kuopio Ischaemic Heart Disease (KIHD) baseline. RESULTS: Men in the highest plasma tHcy concentration quarter had no increase in the risk of coronary events compared with men with lower tHcy concentrations (odds ratio = 0.88, 95% confidence interval 0.44-1.76). Average follow-up time before the first coronary event was 4.9 years (SD 3.2) in men in the highest plasma tHcy quarter and 5.5 years (SD 3.1) in men in the three lowest quarters (P = 0.368). CONCLUSION: We conclude that plasma tHcy is not associated with an increased risk of coronary events in the middle-aged male population in eastern Finland.

Low serum folate concentrations are associated with an excess incidence of acute coronary events: the Kuopio Ischaemic Heart Disease Risk Factor Study.

OBJECTIVE: To test the hypothesis that low serum folate concentrations are associated with an increased risk of acute coronary events in men free of prior coronary heart disease. SETTING: Research Institute of Public Health, University of Kuopio, Kuopio, Finland. DESIGN: Prospective study in a cohort of 734 men aged 46-64 y examined in 1991-1993 as part of the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) and followed for 5 y and 3 months. INTERVENTION: Acute coronary events during the follow-up period were obtained by national hospital discharge registry. Baseline serum folate concentrations were measured by radioimmunoassay. RESULTS: During the follow-up, six (2.5%) men with higher serum folate concentrations (highest third>11.3 nmol/1) and 28 (5.7%) men with lower serum folate (two lowest thirds) developed an acute coronary event (P=0.008). In a Cox model adjusting for age, examination years, and plasma lycopene concentration, in men with higher serum folate concentrations the relative risk for an acute coronary event was 0.31 (95% CI 0.11-0.90, P=0.031) when compared with men with lower serum folates. CONCLUSION: This prospective cohort study in middle-aged men from eastern Finland indicates that moderate-to-high levels of serum folate are associated with a greatly reduced incidence of acute coronary events.

Risk of acute coronary events according to serum concentrations of enterolactone: a prospective population-based case-control study.

BACKGROUND: The lignan enterolactone, produced by the intestinal microflora from dietary precursors, has been implicated in protection against cancer. We investigated the association of serum enterolactone concentration with the risk of acute coronary events in a prospective nested case-control study in middle-aged men from eastern Finland. METHODS: Enterolactone was measured by time-resolved fluoroimmunoassay in serum from 167 men who had an average 7.7 years of follow-up to an acute coronary event and from 167 control men. Both cases and controls were from a cohort of 2005 men who had no clinical coronary heart disease (CHD) at baseline. The controls were matched for age, examination year, and residence. Acute coronary events were registered prospectively. FINDINGS: The mean baseline serum enterolactone concentration was lower among the cases than the controls (18.2 [SD 21.1] vs 23.5 [18.2] nmol/L, p=0.001). The men in the highest quarter of the enterolactone distribution (>30.1 nmol/L) had a 58.8% (95% CI 24.1-77.6, p=0.005) lower risk of acute coronary events than men in the lowest quarter. After adjustment for the nine most strongly predictive risk factors, men in the highest enterolactone quarter had a 65.3% (11.9-86.3, p=0.03) lower risk than men in the lowest quarter. INTERPRETATION: Healthy men with high serum concentrations of enterolactone had a lower risk of acute coronary events than men with lower concentrations. These findings support the hypothesis that plant-dominated fibre-rich food lowers the risk of CHD.