Georg Alfthan

Relation of serum homocysteine and lipoprotein(a) concentrations to atherosclerotic disease in a prospective Finnish population based study

The relation of serum total homocysteine and lipoprotein(a) (Lp(a)) with the incidence of atherosclerotic disease was investigated among 7424 men and women aged 40-64 years free of atherosclerotic disease at baseline in 1977. During the 9-year follow-up, 134 male and 131 female cases with either myocardial infarction or stroke were identified. For each case a control subject was selected belonging to the same sex and 5-year age group. Serum samples collected in 1977 were stored at -20 degrees C and analyzed in 1991. The mean serum homocysteine concentration of male cases and controls was 9.99 mumol/l and 9.82 mumol/l at baseline and that of female cases and controls 9.58 mumol/l and 9.24 mumol/l, respectively. The median serum Lp(a) concentration of male cases and controls was 73 mg/l and 108 mg/l and that of female cases and controls 113 mg/l and 91 mg/l, respectively. The differences between cases and controls were not statistically significant. There was also no significant association between either homocysteine or Lp(a) and atherosclerotic disease, myocardial infarction or stroke in logistic regression analyses. The odds ratios varied from 1.00 to 1.26 for homocysteine and from 0.81 to 1.06 for Lp(a). The results of this prospective population-based study do not support the hypotheses that serum homocysteine or Lp(a) are risk factors for atherosclerotic disease. The lack of association between serum homocysteine and atherosclerotic disease may be due to the exceptionally low gene frequency predisposing to homocysteinemia in Finland.

Association between cardiovascular death and myocardial infarction and serum selenium in a matched-pair longitudinal study

A case-control study was conducted to investigate the association between serum selenium and risk of death from acute coronary heart disease (CHD) as well as risk of fetal and non-fetal myocardial infarction (MI). Case-control pairs came from a population of 11,000 persons examined in 1972 from two counties in eastern Finland, an area with an exceptionally high mortality from cardiovascular diseases. Cases were aged 35-59 years and had died of CHD or other CVD or had a non-fetal MI during a seven-year follow-up. Controls were matched for sex, age, daily tobacco consumption, serum cholesterol, diastolic blood pressure, and history of angina pectoris. The mean serum selenium concentration for all cases was 51.8 micrograms/l and for all controls 55.3 micrograms/l (p less than 0.01). Serum selenium of less than 45 micrograms/l was associated with an adjusted relative risk of CHD death of 2.9 (p less than 0.01, 95% CI, 1.4-6.0), a relative risk of CVD death of 2.2 (p less than 0.01, 95% CI, 1.2-4.0), and a relative risk of fatal and nonfatal MI of 2.1 (p less than 0.001, 95% Ci, 1.4-3.1). 22% (95% CI, 8-35%) of contrary deaths were attributable to serum selenium in the whole study population.

Crossreaction between antibodies to oxidised low-density lipoprotein and to cardiolipin in systemic lupus erythematosus

Serum lipoproteins contain phospholipids and modified low-density lipoprotein (LDL) may thus act as a target for antiphospholipid antibodies. Raised concentrations of IgG antibodies against oxidised LDL were found in 47 of 61 (80%) patients with systemic lupus erythematosus (SLE). 46% of patients also had raised concentrations of IgG anticardiolipin antibodies. Binding of anticardiolipin antibodies to solid-phase cardiolipin was inhibited by oxidised LDL but not by native LDL in 16 of 21 sera from SLE patients. These observations suggest crossreactivity between antiphospholipid antibodies, which are closely associated with thrombosis in SLE, and antibodies to oxidised LDL, thus providing a possible link between thrombotic and atherosclerotic complications in SLE.

Risk of cancer in relation to serum concentrations of selenium and vitamins A and E: matched case-control analysis of prospective data.

The independent and joint associations of serum selenium and vitamin A (retinol) and E (alpha tocopherol) concentrations with the risk of death from cancer were studied in 51 case-control pairs--that is, 51 patients with cancer, each paired with a control matched for age, sex, and smoking. Case-control pairs came from a random sample of some 12000 people aged 30-64 years resident in two provinces of eastern Finland who were followed up for four years. Patients who died of cancer during the follow up period had a 12% lower mean serum selenium concentration (p = 0.015) than the controls. The difference persisted when deaths from cancer in the first follow up year were excluded. The adjusted risk of fatal cancer was 5.8-fold (95% confidence interval 1.2-29.0) among subjects in the lowest tertile of selenium concentrations compared with those with higher values. Subjects with both low selenium and low alpha tocopherol concentrations in serum had an 11.4-fold adjusted risk. Among smoking men with cancer serum retinol concentrations were 26% lower than in smoking controls (p = 0.002). These data suggest that dietary selenium deficiency is associated with an increased risk of fatal cancer, that low vitamin E intake may enhance this effect, and that decreased vitamin or provitamin A intake contributes to the risk of lung cancer among smoking men with a low selenium intake.

Serum fatty acids, apolipoproteins, selenium and vitamin antioxidants and the risk of death from coronary artery disease.

The independent association of serum concentrations of saturated and polyunsaturated fatty acids, apolipoproteins AI and B, selenium and vitamins A and E with the risk of death from coronary artery disease (CAD) was studied in 92 persons with no previous myocardial infarction, who died from CAD during a 5-year follow-up, and their 92 1-to-1 matched controls. Case-control pairs came from a randomly drawn population sample of approximately 12,000 persons aged 30 to 64 years from 2 provinces of eastern Finland, an area with exceptionally high CAD mortality. Control subjects were matched for sex, age, serum cholesterol, mean arterial pressure, tobacco consumption and history of cardiovascular diseases. The persons who died of CAD had lower serum esterified arachidonic acid concentrations before follow-up than the control subjects (41 vs 48 mg/liter, p = 0.05), and this difference was greater for pairs with no chest pain on effort (36 vs 50 mg/liter, p less than 0.05). The adjusted risk of CAD death in persons with a serum polyunsaturated to saturated (P/S) fatty acid ratio of 0.28 or less (in the lowest tertile) was 3.5-fold (95% confidence interval [CI], 1.5 to 8.2) compared with those with higher serum P/s ratios in a multivariate logistic model and 5.6-fold (95% CI 1.6 to 19.8) for pairs with no chest pain on effort. A low serum apolipoprotein AI concentration (1.25 g/liter or less, in the lowest tertile) was associated with a 2.5-fold (95% CI 1.1 to 5.7) adjusted risk of CAD death among the chest pain-free persons.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship of serum selenium and antioxidants to plasma lipoproteins, platelet aggregability and prevalent ischaemic heart disease in Eastern Finnish men

In a cross-sectional population study of 1132 unselected Eastern Finnish men aged 54 years, serum selenium concentration had a weak positive association with plasma HDL cholesterol (standardised partial regression coefficient, beta = 0.061, P = 0.019) and a fairly strong inverse relationship (beta = -0.223, P less than 0.001) with the extent of ADP-induced platelet aggregation. Neither plasma ascorbate concentration nor alpha-tocopherol to total cholesterol ratio had any association with plasma lipoproteins, platelet aggregability or prevalent ischaemic heart disease (IHD). When a covariance-correction was applied, men with ischaemic ECG findings at exercise had a lower mean serum selenium than others (81.5 micrograms/l vs. 85.9 micrograms/l, P less than 0.01 for difference). This difference was equally large for men with neither symptoms nor previous diagnosis of IHD.

Antibodies to Periodontal Pathogens Are Associated With Coronary Heart Disease

Objective—We analyzed the association of coronary heart disease (CHD) and serology of periodontitis in a random sample (n=1163) of men (aged 45 to 74 years) by determining serum IgG-antibodies to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. Methods and Results—CHD (n=159) was more prevalent among edentulous than dentate subjects (19.8% and 12.1%, P =0.003). In the dentate population, CHD was more common among subjects seropositive for P. gingivalis compared with those seronegative (14.0% and 9.7%, P =0.029). Accordingly, CHD was more prevalent in subjects with a high combined antibody response than those with a low response (17.4% and 11.1%, P =0.026). When adjusted for age and several CHD risk factors, the subjects with a high combined antibody response had an odds ratio of 1.5 (95% CI, 0.95 to 2.50, P =0.077) for prevalent CHD. In a linear regression model, the combined antibody response was directly associated with prevalent CHD (P =0.046) and inversely with serum HDL cholesterol concentration (P =0.050). Conclusions—In conclusion, edentulousness and serum antibodies to major periodontal pathogens were associated with CHD. This suggests that periodontal infection or response of the host against the infection may play a role in the pathogenesis of CHD.

Antibodies to periodontal pathogens and stroke risk.

Background and Purpose— The association between cerebrovascular events and periodontitis has been found in few studies based on clinical periodontal examinations. However, evidence on the association between periodontal pathogens and stroke is lacking. Therefore, the aim of the study was to investigate whether elevated levels of serum antibodies to major periodontal pathogens predict stroke in a case–control study. Methods— The study population comprised 6950 subjects (aged 45 to 64 years) who participated in the Mobile Clinic Health Survey in 1973 to 1976 in Finland. During a follow-up of 13 years, a total of 173 subjects had a stroke. From these, 64 subjects had already experienced a stroke or had signs of coronary heart disease (CHD) at baseline, whereas 109 subjects were apparently healthy. Two controls per case were matched for age, gender, municipality, and disease status. Serum IgG and IgA class antibody levels to the periodontal pathogens, Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis, were determined by multiserotype enzyme-linked immunosorbent assay. Results— The cases identified during the follow-up that were free of stroke or CHD at baseline were more often IgA-seropositive for A. actinomycetemcomitans than were their controls, 41.3% versus 29.3%. Compared with the seronegative, the seropositive subjects had a multivariate odds ratio of 1.6 (95% CI, 1.0 to 2.6) for stroke. The patients with a history of stroke or CHD at baseline were more often IgA-seropositive for P. gingivalis than were their controls, 79.7% versus 70.2%. When compared with the seronegative, the seropositive subjects had an odds ratio of 2.6 (1.0 to 7.0) for secondary stroke. Conclusions— The present prospective study provides serological evidence that an infection caused by major periodontal pathogens is associated with future stroke.

Serum Antibody Levels to Actinobacillus actinomycetemcomitans Predict the Risk for Coronary Heart Disease

Objective—The association between serum antibody levels to major periodontal pathogens and coronary heart disease (CHD) was analyzed in a prospective population-based study. Methods and Results—The population comprised 1023 men (aged 46 to 64 years) in the Kuopio Ischemic Heart Disease Study. The subjects with CHD at baseline (n=113) were more often seropositive for Porphyromonas gingivalis IgA (38.9% versus 28.5%, P=0.021) and IgG (60.2% versus 46.7%, P=0.007) than those without CHD. During the 10-year follow-up, 109 men free from CHD at baseline experienced an acute myocardial infarction or CHD death. The men with an end point were more often seropositive for Actinobacillus actinomycetemcomitans IgA (15.5% versus 10.2%, P=0.019) than those who remained healthy. In the highest tertile of A. actinomycetemcomitans IgA-antibodies compared with the lowest one, the relative risk (RR) for an end point adjusted for CHD risk factors was 2.0 (95% confidence interval [CI], 1.2 to 3.3). In the Porphyromonas gingivalis IgA-antibody tertiles, the highest RR of 2.1 (1.3 to 3.4) was observed in the second tertile. All antibody levels correlated positively with the carotid artery intima-media thickness. Conclusions—High-serum antibody levels to major periodontal pathogens are associated with subclinical, prevalent, and future incidence of CHD. Periodontal pathogens or host response against them may contribute to the pathogenesis of CHD.

Plasma concentrations of the flavonoids hesperetin, naringenin and quercetin in human subjects following their habitual diets, and diets high or low in fruit and vegetables.

Objectives: To determine the fasting plasma concentrations of quercetin, hesperetin and naringenin in human subjects consuming their habitual diets, and diets either high or low in fruit and vegetables. To investigate whether plasma concentrations of flavanones can serve as biomarkers of their intake.Design: This was a cross-over, strictly controlled dietary intervention consisting of a 2 week baseline period, and two 5 week dietary periods with a 3 week wash-out period in between. The low-vegetable diet contained few fruit and vegetables and no citrus fruit. The high-vegetable diet provided various fruits and vegetables daily including on average one glass of orange juice, one-half orange and one-half mandarin.Subjects: Thirty-seven healthy females.Results: The high-vegetable diet provided 132 mg of hesperetin and 29 mg of naringenin. The low-vegetable diet contained no flavanones. The mean plasma hesperetin concentration increased from 12.2 nmol/l after the low-vegetable diet to 325 nmol/l after the high-vegetable diet. The respective increase for naringenin was from <73.5 nmol/l for all subjects to a mean value of 112.9 nmol/l. The mean plasma quercetin concentration was 52 nmol/l after the baseline period, during which habitual diets were consumed, and it did not change significantly during the intervention. Interindividual variation in the plasma levels of hesperetin and naringenin was marked and, after the baseline and wash-out periods, and the low-vegetable diet, a majority of the samples had plasma flavanone levels below the limit of detection. After the high-vegetable diet, hesperetin and naringenin were detectable in 54 and 22% of all samples. Quercetin was detectable in nearly all samples after all study periods.Conclusion: Hesperetin, naringenin and quercetin are bioavailable from the diet, but the plasma concentrations of hesperetin and naringenin are poor biomarkers of intake.