Jukka T. Salonen

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.

Association between the functional variant of the catechol-O-methyltransferase (COMT) gene and type 1 alcoholism.

Catechol-O-methyltransferase (COMT) is an enzyme which has a crucial role in the metabolism of dopamine. It has been suggested that a common functional genetic polymorphism in the COMT gene, which results in 3 to 4-fold difference in COMT enzyme activity,1,2 may contribute to the etiology of mental disorders such as bipolar disorder and alcoholism.1 Since ethanol-induced euphoria is associated with the rapid release of dopamine in limbic areas, it is conceivable that subjects who inherit the allele encoding the low activity COMT variant would have a relatively low dopamine inactivation rate, and therefore would be more vulnerable to the development of ethanol dependence. The aim of this study was to test this hypothesis among type 1 (late-onset) alcoholics. The COMT polymorphism was determined in two independent male late onset (type 1) alcoholic populations in Turku (n = 67) and Kuopio (n = 56). The high (H) and low (L) activity COMT genotype and allele frequencies were compared with previously published data from 3140 Finnish blood donors (general population) and 267 race- and gender-matched controls. The frequency of low activity allele (L) was markedly higher among the patients both in Turku (P = 0.023) and in Kuopio (P = 0.005) when compared with the general population. When all patients were compared with the general population (blood donors), the difference was even more significant (P = 0.0004). When genotypes of all alcoholics (n = 123) were compared with genotypes of matched controls, the odds ratio (OR) for alcoholism for those subjects having the LL genotype vs those with HH genotype was 2.51, 95% CI 1.22–5.19, P = 0.006. Also, L allele frequency was significantly higher among alcoholics when compared with controls (P = 0.009). The estimate for population etiological (attributable) fraction for the LL genotype in alcoholism was 13.3% (95% CI 2.3–25.7%). The results indicate that the COMT polymorphism contributes significantly to the development of late-onset alcoholism.

Total and HDL cholesterol and risk of stroke. EUROSTROKE: a collaborative study among research centres in Europe

Background: Controversy remains on the relation between serum lipids levels and stroke risk. This paper investigated the association of total and HDL cholesterol level to fatal and non-fatal, and haemorrhagic and ischaemic stroke in four European cohorts participating in EUROSTROKE. Methods: EUROSTROKE is a collaborative project among ongoing European cohort studies on incidence and risk factors of stroke. EUROSTROKE is designed as a nested case-control study. For each stroke case, two controls were sampled. Strokes were classified according to MONICA criteria or reviewed by a panel of four neurologists. At present, data on stroke and risk factors were available from cohorts in Cardiff (84 cases), Kuopio (74 cases), Rotterdam (157 cases), and Novosibirsk (79 cases). Results: Pooled analyses showed no significant association between total cholesterol and risk of stroke (odds ratio for increase of 1 mmol/l in cholesterol of 0.98 (95% CI 0.88 to 1.09)). Analyses for haemorrhagic stroke and cerebral infarction revealed odds ratios of 0.80 (95% CI 0.61 to 1.05) and 1.06 (95% CI 0.94 to 1.19), respectively. The association of HDL cholesterol to stroke was different in men compared with women. In men, there was a general trend towards a lower risk of stroke with an increase in HDL (odds ratio per 1 mmol/l increase in HDL cholesterol 0.68 (95% CI 0.40 to 1.16)). In women, however, an increase in HDL was associated with a significant increased risk of non-fatal stroke and of cerebral infarction (odds ratios of 2.46 (95% 0.1.20 to 5.04) and 2.52 (95% CI 1.15 to 5.50), respectively. The difference between men and women in the association of HDL with stroke seemed to differ mainly in smokers and never smokers, but not among ex smokers. Conclusion: This analysis of the EUROSTROKE project could not disclose an association of total cholesterol with fatal, non-fatal, haemorrhagic or ischaemic stroke. HDL cholesterol however, seemed to be related to stroke differently in men than in women.

Plasma Vitamin C Modifies the Association Between Hypertension and Risk of Stroke

Background and Purpose— There are no prospective studies to determine whether plasma vitamin C modifies the risk of stroke among hypertensive and overweight individuals. We sought to examine whether plasma vitamin C modifies the association between overweight and hypertension and the risk of stroke in middle-aged men from eastern Finland. Methods— We conducted a 10.4-year prospective population-based cohort study of 2419 randomly selected middle-aged men (42 to 60 years) with no history of stroke at baseline examination. A total of 120 men developed a stroke, of which 96 were ischemic and 24 hemorrhagic strokes. Results— Men with the lowest levels of plasma vitamin C (<28.4 &mgr;mol/L, lowest quarter) had a 2.4-fold (95% CI, 1.4 to 4.3;P =0.002) risk of any stroke compared with men with highest levels of plasma vitamin C (>64.96 &mgr;mol/L, highest quarter) after adjustment for age and examination months. An additional adjustment for body mass index, systolic blood pressure, smoking, alcohol consumption, serum total cholesterol, diabetes, and exercise-induced myocardial ischemia attenuated the association marginally (relative risk, 2.1; 95% CI, 1.2 to 3.8;P =0.01). Adjustment for prevalent coronary heart disease and atrial fibrillation did not attenuate the association any further. Furthermore, hypertensive men with the lowest vitamin C levels (<28.4 &mgr;mol/L) had a 2.6-fold risk (95% CI, 1.52 to 4.48;P <0.001), and overweight men (≥25 kg/m2) with low plasma vitamin C had a 2.7-fold risk (95% CI, 1.48 to 4.90;P =0.001) for any stroke after adjustment for age, examination months, and other risk factors. Conclusions— Low plasma vitamin C was associated with increased risk of stroke, especially among hypertensive and overweight men.

Lycopene, atherosclerosis, and coronary heart disease.

Diets rich in fruits and vegetables containing carotenoids have been of interest because of their potential health benefit against chronic diseases such as cardiovascular diseases (CVD) and cancer. Interest particularly in lycopene is growing rapidly following the recent publication of epidemiological studies that have associated high lycopene levels with reductions in CVD incidence. Two studies were conducted. In the first one, we examined the role of lycopene as a risk-lowering factor with regard to acute coronary events and stroke in the prospective Kuopio Ischemic Heart Disease Risk Factor (KIHD) Study. The subjects were 725 middle-aged men free of coronary heart disease and stroke at the study baseline. In a Coxs proportional hazards model adjusting for covariates, men in the lowest quartile of serum levels of lycopene had a 3.3-fold (P < 0.001) risk of the acute coronary event or stroke as compared with others. In the second study, we assessed the association between plasma concentration of lycopene and intima-media thickness of the common carotid artery wall (CCA-IMT) in a cross-sectional analysis of the Antioxidant Supplementation in the Atherosclerosis Prevention (ASAP) study data in 520 asymptomatic men and women. In a covariance analysis adjusting for common cardiovascular risk factors, low plasma levels of lycopene were associated with an 18% Increase of IMT in men as compared with men in whom plasma levels were higher than median (P = 0.003 for difference). In women, the difference did not remain significant after the adjustments. On the basis of these works, it is evident that the circulating levels of lycopene play some role with regard to cardiovascular health in Finland, at least in men. We conclude that circulating levels of lycopene, a biomarker of tomato-rich food, may play a role in early stages of atherogenesis and may have clinical and public health relevance.

Physical Workload and Risk of Early Retirement: Prospective Population-based Study Among Middle-aged Men

Early retirement produces a heavy economic burden in many western societies. There is a need to identify single risk factors for early retirement and to find methods for preventing it. To estimate the effect of heavy physical work on early retiring, a cohort of 1755 men aged 42 to 65 years from eastern Finland was followed up from 1984 to 2000. Self-estimated physical workload was assessed at baseline. The inclusive pension records were obtained from national pension institutions. Logistic regression modeling was used to estimate the effect of physical workload and single physical risk factors on the risk of disability pension and nonillness-based pension. Risks were estimated for both disease-specific and all disability pensions. The interaction of physical fitness and physical workload and the resulting effects on risk were also estimated. During the follow-up, 861 (49.1%) men retired on a disability pension and 331 men (18.9%) retired on a nonillness-based early pension. Only 273 (15.6%) men reached the age for getting the normal old-age pension without having had any other early pension After adjustment for age, body mass index, alcohol consumption, smoking, maximal oxygen uptake, education and corresponding illness at baseline, heavy physical work was found to be associated with an increased risk of being retired on a disability pension due to musculoskeletal disorders (odds ratio (OR) 2.21, 95% confidence interval 1.36 to 3.61) but not due to cardiovascular or mental diseases. The association was stronger if cardiorespiratory fitness was poor. Lifting, static muscular loading and uncomfortable work positions increased the risk of early retirement especially due to musculoskeletal disorders. Loading of the upper extremity alone or with the neck and shoulder region seems to be an independent risk factor for early retirement. We concluded that physical workload increases the risk of retirement on a disability pension especially due to musculoskeletal disorders. In heavy physical work, the risk is increased especially among men with musculoskeletal or cardiovascular disease and poor cardiorespiratory fitness.

Coenzyme Q10: absorption, antioxidative properties, determinants, and plasma levels.

The purpose of this article is to summarise our studies, in which the main determinants and absorption of plasma coenzyme Q10 (Q10, ubiquinone) have been assessed, and the effects of moderate dose oral Q10 supplementation on plasma antioxidative capacity, lipoprotein oxidation resistance and on plasma lipid peroxidation investigated. All the supplementation trials carried out have been blinded and placebo-controlled clinical studies. Of the determinants of Q10, serum cholesterol, serum triglycerides, male gender, alcohol consumption and age were found to be associated positively with plasma Q10 concentration. A single dose of 30 mg of Q10, which is the maximum daily dose recommended by Q10 producers, had only a marginal elevating effect on plasma Q10 levels in non-Q10-deficient subjects. Following supplementation, a dose-dependent increase in plasma Q10 levels was observed up to a daily dose of 200 mg, which resulted in a 6.1-fold increase in plasma Q10 levels. However, simultaneous supplementation with vitamin E resulted in lower plasma Q10 levels. Of the lipid peroxidation measurements, Q10 supplementation did not increase LDL TRAP, plasma TRAP, VLDL+LDL oxidation resistance nor did it decrease LDL oxidation susceptibility ex vivo. Q10 with minor vitamin E dose neither decreased exercise-induced lipid peroxidation ex vivo nor muscular damage. Q10 supplementation might, however, decrease plasma lipid peroxidation in vivo, as assessed by the increased proportion of plasma ubiquinol (reduced form, Q10H 2 ) of total Q10. High dose vitamin E supplementation decreased this proportion, which suggests in vivo regeneration of tocopheryl radicals by ubiquinol.

Association between low serum enterolactone and increased plasma F2-isoprostanes, a measure of lipid peroxidation

Evidence suggests that low serum enterolactone concentration might be an independent risk factor for acute coronary events. Enterolactone is a lignan, which is formed by intestinal bacteria from precursors in plant foods. Due to the biphenolic structure of enterolactone, it could act as an antioxidant and through this contribute to cardiovascular health. The aim of this study was to test the hypothesis that a low serum enterolactone concentration is associated with increased in vivo lipid peroxidation, assessed by plasma F2-isoprostane concentrations. We investigated this association in a subset of participants in The Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study. Out of 256 male participants a subsample of 100 consecutive men from baseline was selected for F2-isoprostane assays. The mean serum enterolactone concentration was 16.6 nmol/l and that of F2-isoprostanes 29.6 ng/l. The correlation coefficient for association between serum enterolactone and F2-isoprostane concentrations was -0.30 (P<0.003). Plasma F2-isoprostane levels decreased linearly across quintiles of serum enterolactone concentration (P=0.008 for a linear trend). In a multivariate model, enterolactone persisted as a significant predictor after adjustment for vitamins and other variables, with the strongest associations with F2-isoprostanes. Our present data suggest that low serum enterolactone concentration is associated with enhanced in vivo lipid peroxidation in men.

Gamma-glutamyltransferase and risk of stroke: the EUROSTROKE project

Background: Alcohol consumption has been implicated in the aetiology of stroke. As data on alcohol consumption obtained by questionnaire are susceptible to missclassification, this study evaluated the assocation between γ-glutamyltransferase (γ-GT), as a marker for alcohol consumption, and fatal, non-fatal, haemorrhagic and ischaemic stroke in three European cohort studies, participating in EUROSTROKE. Methods: EUROSTROKE is a collaborative project among ongoing European cohort studies on incidence and risk factors of stroke. EUROSTROKE is designed as a nested case-control study. For each stroke case, two controls were sampled. Strokes were classified according to MONICA criteria or reviewed by a panel of four neurologists. At present, data on stroke and γ-GT were available from cohorts in Cardiff (57 cases), Kuopio (66 cases), and Rotterdam (108 cases). Results: An increase in γ-GT of one standard deviation (28.7 IU/ml) was associated with an age and sex adjusted 26% (95% CI 5 to 53) increase in risk of stroke. Adjustment for confounding variables such as drug use, history of myocardial infarction, total cholesterol, and diabetes mellitus did not materially attenuate the association. The risk of haemorrhagic stroke increased linearly with increase in γ-GT. The association for cerebral infarction was not graded: the risk increased beyond the first quartile, and remained increased. The association of γ-GT with stroke was significantly stronger among subjects without diabetes mellitus compared with subjects with diabetes mellitus (no association observed). Conclusion: This EUROSTROKE analysis showed that an increased γ-GT, as a marker of alcohol consumption, is associated with increased risk of stroke, in particular haemorrhagic stroke.

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 46–64u2005y examined in 1991–1993 as part of the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) and followed for 5u2005y 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>11.3u2005nmol/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