Tiina H. Rissanen

Six-Year Effect of Combined Vitamin C and E Supplementation on Atherosclerotic Progression The Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) Study

Background—Self-selected supplementation of vitamin E has been associated with reduced coronary events and atherosclerotic progression, but the evidence from clinical trials is controversial. In the first 3 years of the ASAP trial, the supplementation with 136 IU of vitamin E plus 250 mg of slow-release vitamin C twice daily slowed down the progression of carotid atherosclerosis in men but not women. This article examines the 6-year effect of supplementation on common carotid artery (CCA) intima-media thickness (IMT). Methods and Results—The subjects were 520 smoking and nonsmoking men and postmenopausal women aged 45 to 69 years with serum cholesterol ≥5.0 mmol/L (193 mg/dL), 440 (84.6%) of whom completed the study. Atherosclerotic progression was assessed ultrasonographically. In covariance analysis in both sexes, supplementation reduced the main study outcome, the slope of mean CCA-IMT, by 26% (95% CI, 5 to 46, P =0.014), in men by 33% (95% CI, 4 to 62, P =0.024) and in women by 14% (not significant). In both sexes combined, the average annual increase of the mean CCA-IMT was 0.014 mm in the unsupplemented and 0.010 mm in the supplemented group (25% treatment effect, 95% CI, 2 to 49, P =0.034). In men, this treatment effect was 37% (95 CI, 4 to 69, P =0.028). The effect was larger in subjects with either low baseline plasma vitamin C levels or CCA plaques. Vitamin E had no effect on HDL cholesterol. Conclusions—These data replicate our 3-year findings confirming that the supplementation with combination of vitamin E and slow-release vitamin C slows down atherosclerotic progression in hypercholesterolemic persons.

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

BackgroundPrevious 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 ResultsWe 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 &mgr;g/g) had a 67% reduced risk (P=0.016) of acute coronary events compared with men in the lowest fifth who had a high hair content of mercury (>2.0 &mgr;g/g). There was no association between proportion of eicosapentaenoic acid and the risk of acute coronary events. ConclusionsOur 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.

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.

Abstract. Salonen JT, Nyyssönen K, Salonen R, Lakka H‐M, Kaikkonen J, Porkkala‐Sarataho E, Voutilainen S, Lakka TA, Rissanen T, Leskinen L, tuomainen T‐P, Valkonen V‐P, Ristonmaa U (University of Kuopio, Finland), Poulsen HE (University of Copenhagen, Copenhagen, Denmark). 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. J Intern Med 2000; 248: 377–386.

Mercury, Fish Oils, and Risk of Acute Coronary Events and Cardiovascular Disease, Coronary Heart Disease, and All-Cause Mortality in Men in Eastern Finland

Objective— 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. Methods and Results— 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 &mgr;g/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. Conclusions— 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.

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 B6, and vitamin B12 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 B6 had no significant association and that of vitamin B12 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.

Serum fatty acid composition predicts development of impaired fasting glycaemia and diabetes in middle-aged men.

Aims Dietary fatty acid intake is reflected in serum fatty acid composition. Studies prospectively investigating serum fatty acids and development of impaired fasting glycaemia (IFG) or diabetes mellitus (DM) are largely lacking. We assessed the association of serum fatty acid composition with development of IFG or DM.

Low Plasma Lycopene Concentration Is Associated With Increased Intima-Media Thickness of the Carotid Artery Wall

Abstract—Although a number of epidemiological studies have evaluated the association between &bgr;-carotene and the risk of cardiovascular diseases, there has been little research on the role of lycopene, an acyclic form of &bgr;-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 &mgr;mol/L in men and 0.15 &mgr;mol/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.

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.European Journal of Clinical Nutrition (2000) 54, 424–428

Effects of Astaxanthin Supplementation on Lipid Peroxidation

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.

Serum linoleic and total polyunsaturated fatty acids in relation to prostate and other cancers: A population‐based cohort study

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.