R. Salonen

Oxidative modification of LDL renders it immunogenic and autoantibodies to epitopes of oxidised LDL, such as malondialdehyde (MDA)-lysine, are found in serum and recognise material in atheromatous tissue. However, there has been no prospective study to assess the importance of oxidised LDL among patients with vascular disease. We compared the titre of autoantibodies to MDA-modified LDL and native LDL in baseline serum samples of 30 eastern Finnish men with accelerated two-year progression of carotid atherosclerosis and 30 age-matched controls without progression. Neither group had specific antibody binding to native LDL. A titre was defined as a ratio of antibody binding to MDA-LDL/binding to native LDL. Cases had a significantly higher titre to MDA-LDL (2.67 vs 2.06, p = 0.003). Cases also had a greater proportion of smokers (37% vs 3%), higher LDL cholesterol (4.2 mmol/l vs 3.6 mmol/l), and higher serum copper concentration (1.14 mg/l vs 1.04 mg/l). Even after adjusting for these variables and the severity of baseline atherosclerosis, the difference in antibody titre remained significant in a multifactorial logistic model (p = 0.031). Thus, the titre of autoantibodies to MDA-LDL was an independent predictor of the progression of carotid atherosclerosis in these Finnish men. Our data provide further support for a role of oxidatively modified LDL in atherogenesis.

OBJECTIVE: To investigate whether low vitamin E status is a risk factor for incident non-insulin dependent diabetes mellitus. DESIGN: Population based follow up study with diabetes assessed at baseline and at four years. SETTING: Eastern Finland. SUBJECTS: Random sample of 944 men aged 42-60 who had no diabetes at the baseline examination. INTERVENTION: Oral glucose tolerance test at four year follow up. MAIN OUTCOME MEASURES: A man was defined diabetic if he had either (a) a fasting blood glucose concentration > or = 6.7 mmol/l, or (b) a blood glucose concentration > or = 10.0 mmol/l two hours after a glucose load, or (c) a clinical diagnosis of diabetes with either dietary, oral, or insulin treatment. RESULTS: 45 men developed diabetes during the follow up period. In a multivariate logistic regression model including the strongest predictors of diabetes, a low lipid standardised plasma vitamin E (below median) concentration was associated with a 3.9-fold (95% confidence interval 1.8-fold to 8.6-fold) risk of incident diabetes. A decrement of 1 mumol/l of uncategorised unstandardised vitamin E concentration was associated with an increment of 22% in the risk of diabetes when allowing for the strongest other risk factors as well as serum low density lipoprotein cholesterol and triglyceride concentrations. CONCLUSIONS: There was a strong independent association between low vitamin E status before follow up and an excess risk of diabetes at four years. This supports the theory that free radical stress has a role in the causation of non-insulin dependent diabetes mellitus.

Because high body iron stores have been suggested as a risk factor for acute myocardial infarction, donation of blood could theoretically reduce the risk by lowering body iron stores. For this reason, the authors tested the hypothesis that voluntary blood donation is associated with reduced risk of acute myocardial infarction in a prospective epidemiologic follow-up study in men from eastern Finland. The subjects are all participants of the Kuopio Ischaemic Heart Disease Risk Factor Study. A cohort of 2,862 men aged 42-60 years were followed for an average of almost 9 years. One man (0.7%) out of 153 men who had donated blood in 24 months preceding the baseline examination experienced an acute myocardial infarction during 1984 to 1995, whereas 316 men (12.5%) of 2,529 non-blood donors had an acute myocardial infarction (p < 0.0001 for difference between proportions). In a Cox proportional hazards model adjusting for age, examination years and all other predictive coronary disease risk factors, blood donors had a 88% reduced risk (relative hazard = 0.12, 95% confidence interval 0.02-0.86, p = 0.035) of acute myocardial infarction, compared with non-blood donors. These findings suggest that frequent blood loss through voluntary blood donations may be associated with a reduced risk of acute myocardial infarction in middle-aged men.

OBJECTIVES: This study examined whether heightened cardiovascular reactivity and low socioeconomic status had synergistic effects on the progression of carotid atherosclerosis in a population of eastern Finnish men. METHODS: Data from the Kuopio Ischemic Heart Disease Risk Factor Study were used to measure 4-year progression of intima-media thickness in 882 men according to cardiovascular reactivity and socioeconomic status. Associations were examined in relation to risk factors and were stratified by baseline levels of atherosclerosis and prevalent ischemic heart disease. RESULTS: The effect of reactivity on atherosclerotic progression depended on socioeconomic status. Men who had heightened cardiovascular responsiveness to stress and were born into poor families, received little education, or had low incomes had the greatest atherosclerotic progression. CONCLUSIONS: An understanding of associations between individual risk factors and disease should be based on etiologic hypotheses that are conceived at the population level and involve fundamental social and economic causes of disease. This study demonstrates how examining the interaction of an individual biological predisposition will low socioeconomic status over the life course is etiologically informative for understanding the progression of atherosclerotic vascular disease.

The association between five socioeconomic indices (lifetime occupation, education, income, ownership of material possessions, and childhood socioeconomic status) and plasma fibrinogen levels was investigated in middle-aged Finnish men who were part of the Kuopio Ischemic Heart Disease Risk Factor Study. The Kuopio Ischemic Heart Disease Risk Factor Study is based on a representative age-stratified sample of 2,682 men aged 42, 48, 54, and 60 years. The data were collected between 1984 and 1989. The present analysis is restricted to the 2,011 men for whom information on fibrinogen and all covariates was available. The covariates were alcohol consumption, body mass index, physical fitness, smoking, coffee consumption, high density lipoprotein cholesterol, low density lipoprotein cholesterol, blood leukocyte count, and prevalent disease (at least one sign of ischemic heart disease, hypertension, diabetes, or previous stroke). An age-adjusted inverse association was found between levels of plasma fibrinogen and four of the five socioeconomic indices: current income, education, lifetime occupation status, and current material possessions. After adjustment for the covariates, the association persisted for education, current income, and lifetime occupation. Analysis of the joint effect of childhood and adult socioeconomic status indicated that those who were economically disadvantaged at both times had the highest fibrinogen levels, but the fibrinogen levels of those who were not poor as adults had no variation by childhood socioeconomic status.