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Patients with arthritis who carry the rheumatoid factor (RF) or those who test positive for RF but do not have arthritis (false positive) may have shorter life expectancies than the general population. RF is an antibody frequently found in the blood of adult patients with rheumatoid arthritis. Doctors performed a series of diagnostic tests, including RF screening, on 3,434 volunteers identified with muscle or bone diseases. They followed the group over a period of 13 to 15 years and recorded dates and causes of death for the participants. More participants with a positive or false positive RF test died during this time period as compared to the whole group. There was a higher risk of death due to heart disease in participants with a false positive RF test. There was no correlation between life expectancy and a negative RF test in participants with arthritis.

The study aimed to reveal associations between dietary antioxidant vitamins and other personal characteristics.

Marniemi J, Maatela J, Järvisalo J, Reunanen, A, Mäki J, Tikkanen M J. Health-based reference values of the Mini-Finland health survey: 3. Triglycerides in total serum and in different lipoprotein fractions. Scand J Clin Lab Invest 1994; 54: 43-50.The reference values for triglyceride concentrations in total serum and in its VLDL, LDL and HDL fractions have been produced based on the data obtained in the Mini-Finland Health Survey. The lipoprotein fractions were separated with ultracentrifugation. Efforts were made to obtain reference values for the healthy ambulatory population. Two health-derived selection criteria were used for inclusion of persons into the reference population: those based on the literature available and those based on the recommendations published by the Committee on Reference Values of the Scandinavian Society for Clinical Chemistry and Clinical Physiology, with minor modifications. The frequency distributions of triglycerides especially in total serum and in VLDL fraction were very skewed. Because of that the data were transformed before the calculation of the reference ranges according to the method of Box and Cox [1]. This transformation method appeared to be the best one of many tested methods in obtaining the distributions closer to the normal ones. The 95% inner reference intervals of total serum triglycerides in all subjects and in the two selection groups were 0.5-4.0, 0.5-2.8, and 0.5-3.2 mmol -1 for men and 0.5-3.4, 0.5-2.3, and 0.5-2.4 mmol l-1 for women, respectively. The age dependence of triglyceride level was prominent in women after the early middle age. The distribution and age dependence of VLDL triglycerides resembled those of total triglycerides. In LDL and HDL fractions the skewness was not as clear as in the whole serum or in VLDL fraction. Of the background lifestyle factors obesity, alcohol consumption, smoking and physical exercise had negligible effects on triglyceride reference values.

Maatela J, Marniemi J, Reunanen A, Järvisalo J, Mäki J, Tikkanen M J. Health-based reference values of the Mini-Finland Health Survey: 2. Cholesterol in total serum and in different lipoprotein fractions. Scand J Clin Lab Invest 1994; 54: 33-42.The reference values for cholesterol concentrations in the whole serum and in its VLDL, LDL and HDL fractions have been produced based on the data obtained in the Mini-Finland Health Survey. The lipoprotein fractions were separated with ultracentrifugation. The aim was to obtain reference values for the apparently healthy, ambulatory population. Two health-derived criteria were used to select subjects for reference populations: those based on the literature available and those based on the recommendations published by the Committee on Reference Values of the Scandinavian Society for Clinical Chemistry and Clinical Physiology, with slight modifications.The 95% inner reference intervals of total serum cholesterol in all the subjects and in the two selection groups were 4.2-9.0, 4.2-8.4, and 4.2-8.5mmoir' for men, and 4.2-9.4, 4.1-8.6, and 4.2-9.0mmoll-1 for women, respectively. The corresponding medians were 6.3, 6.2 and 6.2mmoll-1 in men, and 6.4, 6.0 and 6.1mmoll-1 in women, respectively. Frequency distribution curves showed clear skewness to the right in VLDL cholesterol and slight skewness in LDL and HDL cholesterol. In women there was a clear rise in total, VLDL and LDL cholesterol after the early middle age, whereas HDL cholesterol was lower in the older age groups. In men the age dependency was not as prominent; total cholesterol levels showed lower levels in older men.Of the background lifestyle factors alcohol consumption, smoking, obesity and physical exercise had negligible associations with total, VLDL, LDL and HDL cholesterol reference intervals.

The associations between serum alpha-tocopherol, beta-carotene, retinol, retinol-binding protein, and selenium levels and the subsequent occurrence of different cancers of low incidence were investigated in a nested case-control study of 39,268 men and women participating in the Social Insurance Institution's Mobile Clinic Health Examination Survey in Finland. During follow-up from the baseline in 1968-1972 to the end of 1977, a total of 115 cancers of the lip, oral cavity, pharynx, larynx, esophagus, liver, gallbladder, kidney, urinary bladder, brain, and skin were reported to the nationwide Finnish Cancer Registry. Alpha-tocopherol, beta-carotene, retinol, retinol-binding protein, and selenium concentrations were determined from stored serum samples collected from these cancer cases and matched controls at baseline. Several sites indicated an elevated risk of cancer at low levels of the serum variables, although only a few of these associations were statistically significant. Only melanoma patients had significantly lower serum alpha-tocopherol and beta-carotene levels than corresponding controls. Since the numbers of cancer cases were small, no firm conclusions can be drawn from these results until they have been confirmed in studies based on larger cohorts or on pooled data from several small samples.

Prevalence and incidence of known diabetes mellitus in Finnish subjects aged 30 years or over in 1970-1987 were investigated using a nationwide register of drug recipients and four population surveys. On the basis of the drug-register data, the prevalence of drug-treated diabetes in men increased from 1.5% in 1970 to 2.8% in 1987. In women, the prevalence increased from 2.1% in 1970 to 3.0% in 1979 and declined thereafter slightly to 2.7% in 1987. The increase in the prevalence of drug-treated diabetes was mainly due to the increase of diabetes in the age groups 60 years and older. The prevalence of all known diabetic subjects in the population studies increased from 2.1% in the health examination survey of 1966-1972 (n = 38,676) to 3.5% in the interview survey of 1976 (n = 10,657) and to 4.5% in the health examination survey of 1979-1980 (n = 7,217) but decreased to 3.3% in the interview survey in 1987 (n = 9,522). The increased prevalence of obesity in men and better survival may be important factors contributing to the increasing prevalence rates of diabetes in Finnish subjects aged 30 years and over.

From 1968 to 1977, the association between the level of vitamin A in serum and the subsequent incidence of cancer was examined in a longitudinal study of 36,265 persons initially aged 15-99 years in 25 population groups in Finland. During a mean follow-up of 8 years, 766 cancers were diagnosed. Serum retinol, retinol-binding protein, and beta-carotene levels were measured from frozen serum samples (stored at -20 degrees C) drawn from these persons before the start of follow-up and from 1,419 controls matched for sex, age, and place of residence who did not develop cancer during follow-up. The mean level of serum retinol among the cancer cases was 645 micrograms/liter for men and 587 micrograms/liter for women. The corresponding levels in the controls were 3.3% and 2.8% higher. There was an inverse gradient between serum retinol level and the occurrence of cancer among men. This association was, however, mainly concentrated in the first 2 years of follow-up. The mean level of serum beta-carotene was 72.3 micrograms/liter among male cases and 119.5 micrograms/liter among female cases. The corresponding levels of the controls were 14.0% and 5.5% higher. The differences were particularly clear with regard to lung cancer. These findings suggest that the association between retinol and cancer may be due to preclinical cancer and that there may be an association between beta-carotene and cancer.

The Mini-Finland Health Survey was designed to analyse the epidemiology of major public health problems. The study covered a representative sample of the Finnish population aged 30 years or over, and initially comprised 8 000 people. Serum rheumatoid factor was determined in 7 124 cases (89%). There were 138 cases of clinical arthritis in the series, corresponding to a prevalence of 1.9% (1.0% in males and 2.7% in females). Fifty-nine of the cases (0.8% of the population) were seropositive, and 50 cases (0.7%) had in their hand radiographs changes characteristic of rheumatoid arthritis. Twelve of the X-ray positive cases were seronegative. One-half of these proved to be seroconversion cases or rheumatoid variants typically seronegative, such as early-onset juvenile rheumatoid arthritis.

The association between serum alpha-tocopherol levels and the subsequent incidence of cancer was investigated in a longitudinal study of 21,172 men initially aged 15-99 years in six geographic areas in Finland. The baseline examination was conducted in 1968-1972, and during the follow-up of 6-10 years, 453 cancers were diagnosed. The serum alpha-tocopherol levels were measured from stored serum samples from these men and from 841 male controls, matched for municipality and age, who did not develop cancer during the follow-up. The mean levels of serum alpha-tocopherol among the cancer cases and controls were 8.02 and 8.28 mg/liter, respectively. A high serum alpha-tocopherol level was associated with a reduced risk of cancer. The relative risk of cancer in persons in the two highest (threshold 8.70 mg/liter) quintiles of serum alpha-tocopherol was 0.64 (95 per cent confidence interval = 0.49-0.85) in comparison with those in the three lowest quintiles. The association was strongest for the combined group of cancers unrelated to smoking and varied between subgroups of the study population as well as between different cancers. The association persisted when adjusted for serum cholesterol, serum vitamin A, serum selenium, and various confounding factors. It also persisted when subjects with possible signs of cancer at the time when the blood samples were drawn or with cancers diagnosed during the first two years of follow-up were excluded. These findings agree with the hypothesis that high vitamin E intake protects against cancer.

The relationship between serum ceruloplasmin level and cancer incidence was investigated in a case-control study nested within a longitudinal study of 39,268 Finns participating in the Social Insurance Institution's Mobile Clinic Health Examination Survey carried out in 1968-1972. During a median follow-up of 8 years, 766 cancer cases were identified. Ceruloplasmin levels were determined from stored serum samples collected at the baseline from these cancer cases and from two matched controls per case. The overall incidence of cancer was positively associated with serum ceruloplasmin level. The association was strongest for lung cancer and other cancers related to smoking and, consequently, in males. The smoking-adjusted relative risk of lung cancer among men was 4.3 (95% confidence interval (CI) = 1.8-10.6) in the highest quintile of serum ceruloplasmin as compared with that in the lowest quintile. The corresponding relative risks for cancers related to smoking combined, and for cancers not related to smoking were 3.9 (CI = 1.9-8.4) and 0.9 (CI = 0.6-1.5), respectively. The elevated risk of lung cancer at high concentrations of serum ceruloplasmin persisted after further adjustment for several potential confounding factors such as serum levels of vitamins A and E and selenium. The risk was stronger during the first 6 years of follow-up than later, and strongest during the first 2 years. The most likely explanation of the present results thus is that high serum ceruloplasmin levels in lung cancer are mainly due to occult cancer.

Circulating thyroglobulin antibodies (TgA) were detected in 7.9 % and thyroid microsomal antibodies (MsA) in 25.8 % of a sample of 507 subjects in the adult population of southern Finland when titres as low as 1/5 for TgA and 1/10 for MsA were included. Both antibodies were measured by passive haemagglutination techniques. The prevalence of high titres was 0.6 % for TgA (≥ 1/25 000) and 4.2% for MsA (≥ 1/100 000). Eightyeight per cent of the TgA positive subjects also had MsA. The MsA titres were usually markedly higher than those of TgA in the same subjects.Serum thyrotrophin (TSH), cholesterol and triglycerides were measured in 123 euthyroid subjects with thyroid antibodies and no history of thyroid diseases, and in controls matched for age and sex. Serum TSH was elevated in 31 % of the TgA positive subjects and the mean TSH concentration was significantly above that of the controls. All 3 subjects with high TgA titres also had elevated TSH levels. Serum TSH concentration was increased also in 25 % of those with MsA and the mean TSH value was significantly above the control level. High MsA titres were found in 19 subjects and the serum TSH was elevated in 10 of them (53%). The prevalence of symptomless autoimmune thyroiditis (SAT) was 2 and 5 %, of the population when high titres of either TgA or MsA, respectively, and elevation of serum TSH was used as criteria. This fits with our previous observations. There was no difference in serum cholesterol or triglycerides in the TgA or MsA positive subjects or in the corresponding matched controls.

The reference values for gamma-glutamyltransferase (GT), aspartate aminotransferase (ASAT) and alkaline phosphatase (AFOS) activities in serum have been produced on the basis of measurements done in the Mini-Finland Health Survey. A representative sample of all Finns aged 30 years or over comprised 8000 persons, of whom 99.2% participated in the actual health survey. Every effort was made to obtain reference values for the healthy ambulatory population. Three separate health-derived selection criteria were used to obtain such reference values for the above-mentioned enzymes: those based on the available literature, with minor modifications, the recommendations published by the Committee on Reference Values of the Scandinavian Society for Clinical Chemistry and Clinical Physiology, criteria that were obtained after subgroup comparisons of the obtained data, where all the factors affecting the enzyme levels were identified. The recommendations of the Expert Panel on Theory of Reference Values (1987) were strictly adhered to in the statistical analyses. The distribution of the serum activity of GT was very skewed. The overall intervals for men and women were 5.1-1460 and 4.7-748 U/l, respectively. The frequency distributions could be transformed to the normal ones logarithmically. The 95% inner reference intervals for GT in the three groups were 7-76, 7-65, and 8-57 U/l for men and 6-35, 6-30 and 6-32 U/l for women, respectively. For ASAT the full intervals of the enzyme levels in serum were 2.6-770 U/l for men and 8.3-172 U/l for women. After logarithmic transformation the respective reference intervals in the three selection groups were 14-42, 14-40 and 13-39 U/l for men and 13-33, 12-31 and 13-33 U/l for women. The full intervals of AFOS were 47.5-2755 and 5.4-816 U/l for men and women, respectively; after the logarithmic transformation the reference intervals of the three selection groups were 98-267, 97-254 and 97-264 U/l for men and 77-265, 75-231 and 75-250 U/l for women, respectively.

The liver blood flow in non-pregnant women (15 cases) and in late pregnancy (20 cases) was studied by colloidal heat-denatured serum albumin labelled with 131I. The dose used was 10 μCi. The results were evaluated visually by gamma camera or two collimated detectors one of which was directed to the vessels of the thigh and the other placed over the right lobe of the liver. In addition, blood samples were drawn at fixed intervals and their radioactivity was measured. Using previously developed mathematical formulae, the half-time of plasma activity was found to be 2.0 ± 0.4 min in the control group, 2.0 ± 1.1 min in normal pregnancy and 3.0 ± 1.1 min in toxaemia. Because of the great individual variation no significant changes between the groups were demonstrable. The isotope diagnostic method used was found to be suitable for measurement of the hepatic blood flow of patients with a stable liver disease, but because of the changing vital functions and the individual variations during pregnancy this method does not bring out the changes between non-pregnant cases and late pregnancy.

Levels of haemostatic variables that may be involved in thrombogenesis have been compared in groups of men of similar mean age in communities at very low (Gambia), high (England and Czechoslovakia) or very high (Scotland and Finland) risk of ischaemic heart disease (IHD). There was a consistent gradient of higher factor VII levers with higher IHD risk and also suggestive gradients in the case of two other vitamin K dependent factors, factors II and X. Mean platelet counts were lower and mean fibrinolytic activity was greater in Gambian men than in European men. There was a suggestive though not entirely consistent association between mean fibrinogen levels and IHD risk in the groups from IHD-endemic countries. The results as a whole, and particularly those on factor VII, strengthen the case for the increasingly detailed epidemiological as well as laboratory investigation of the role of the haemostatic system in thrombogenesis and IHD.