Reliability of perceived health by sex and age.

The aim of this study was to assess the test-retest reliability of a measure of perceived general health by sex and age. The study analyzed data from the nationally representative Mini-Finland Health Survey of 8000 adults aged 30 and over. The subjects were invited to attend a personal health interview and a health examination in 1978-1980. Altogether 7217 persons participated. Perceived general health was measured at the personal health interview and in the self-administered questionnaire 1-6 weeks apart. The identical questions were: how would you assess your current health? The response alternatives were good, fairly good, intermediate, fairly poor, poor and cannot say. This study showed that among men and women unweighted agreement of the 'good-intermediate-poor' categorization of perceived health was around 70% and unweighted kappa-values were around 0.5. Only in the oldest age-group (75+) reliability declined below these levels. The fair or good reliability of perceived health observed in this study gives additional confidence for using this general measure of overall health status in future research.

Sero-epidemiological association between human-papillomavirus infection and risk of prostate cancer.

Some epidemiological studies of prostate cancer have suggested the existence of a sexually transmitted risk factor, and some studies have reported the presence of human papillomavirus (HPV) DNA in prostate-cancer tissue. To perform a sero-epidemiological evaluation of whether HPV infection is associated with increased risk for prostate cancer, we performed a nested case-control study within a serum bank containing samples from 20,243 healthy Finnish men. We identified 165 cases of prostate cancer that were diagnosed up to 24 years after donation of the serum sample. Two control subjects per case were selected, matched for gender, age and municipality of residence. Serum samples were analyzed for the presence of IgG antibodies against 4 HPV types and against Chlamydia. The presence of antibodies against HPV type 18 was associated with a 2.6-fold increased risk of developing prostate cancer during follow-up (p < 0.005). HPV type 16 tended to be associated with subsequent prostate-cancer occurrence (relative risk: 2.4, p = 0.06), whereas seropositivity for HPV type 11 or type 33 or for Chlamydia was not associated with risk. The results suggest that infection with oncogenic HPV might be involved in the etiology of a minority of prostate cancers.

Elevated lung cancer risk among persons with depressed mood.

Although it has been hypothesized that depressive persons have an excess risk of cancer, few prospective data are available. The association between depressiveness and subsequent incidence of lung cancer was studied in the nationally representative Mini-Finland Health Survey. The study population comprised 7,018 adult men and women, free from cancer at the baseline, carried out in 1978-1980. During a 14-year follow-up, 605 cancer cases occurred, of which 70 were male lung cancer patients. Mental problems and disorders were assessed at the baseline examination using standard interview techniques (General Health Questionnaire and Present State Examination). The relative risk of lung cancer between depressive persons and individuals with a normal depressiveness score was 3.32 (95% confidence interval 1.53-7.20). Neither adjustment for the potential confounding factors of age, education, geographic area, smoking, alcohol consumption, body mass index, serum cholesterol, leisure-time exercise, general health, and use of antidepressant medication nor exclusion of cancer cases occurring during the first 4 years of follow-up notably altered the results. There was a strong interaction between depressiveness and smoking. The relative risks of lung cancer between smokers and nonsmokers were 3.38 (95% confidence interval 1.09-10.52) at normal depressiveness score levels and 19.67 (95% confidence interval 2.57-150.7) at strongly elevated levels, respectively. It is possible that depressiveness modifies the effect of smoking on lung cancer risk either by biologic mechanisms or by affecting smoking behavior.

Serum calcium, magnesium, copper and zinc and risk of cardiovascular death.

OBJECTIVE: To study the association of serum calcium, magnesium, copper and zinc concentrations with cardiovascular mortality. DESIGN: A nested case-control study within a prospective population study. SUBJECTS AND METHODS: 230 men dying from cardiovascular diseases and 298 controls matched for age, place of residence, smoking and follow-up time. Mean follow-up time was 10 years. Serum calcium, magnesium, copper and zinc concentrations were determined from samples kept frozen at -20 degrees C. RESULTS: High serum copper and low serum zinc concentrations were significantly associated with an increased mortality from all cardiovascular diseases and from coronary heart disease in particular. The relative risk of coronary heart disease mortality between the highest and lowest tertiles of serum copper and zinc were 2.86 (P = 0.03) and 0.69 (P = 0.04), respectively. Adjustment for social class, serum cholesterol, body mass index, hypertension and known heart disease at baseline examination did not materially alter the results. No significant differences were observed in concentrations of serum calcium and magnesium between cases and controls. CONCLUSIONS: High serum copper and low serum zinc are associated with increased cardiovascular mortality whereas no association was found with serum calcium and magnesium and mortality risk.

Circulating anti-Helicobacter pylori immunoglobulin A antibodies and low serum pepsinogen I level are associated with increased risk of gastric cancer.

Helicobacter pylori infection has been suggested to be associated with an increased risk of gastric cancer, and low levels of serum pepsinogen I (PG I) have been linked to atrophic gastritis, which is a risk factor for gastric cancer. In Finland, 39,268 persons from 25 cohorts participated during 1968-1972 in a health examination survey and were followed for up to 13 years. A nested case-control study was performed on 84 stomach cancer patients identified from the Finnish Cancer Registry and 146 controls matched for age, sex, and municipality. Serum samples drawn at the baseline study were analyzed. An elevated level of serum anti-H. pylori immunoglobulin A (IgA) antibodies (a titer > or = 70) and a low serum PG I level ( < 49 micrograms/liter) were associated with an increased risk of gastric cancer. The odds ratios were 2.52 (95% confidence interval (CI) 1.14-5.57) for high IgA and 2.68 (95% CI 1.35-5.30) for low PG I. For high immunoglobulin G (IgG) ( > or = 700), the odds ratio was only 1.50 (95% CI 0.70-3.22). When both high IgA and low PG I were present, the odds ratio was 5.96 (95% CI 2.02-17.57). The association of H. pylori infection with cancer became stronger with longer follow-up times, whereas that of low PG I was strongest at shorter follow-up times. Our findings support the hypothesis that H. pylori infection is a prevalent and potentially preventable cause of gastric cancer. They stress the value of IgA antibody determinations and provide new evidence for a pathogenesis leading from prolonged infection through atrophic gastritis to gastric cancer.

Serum p53 accumulation and altered antibody responses to Epstein-Barr virus proteins precede diagnosis of haemopoietic malignancies of lymphoid origin.

We analysed antibodies to Epstein-Barr virus nuclear antigens (EBNAs 1, 2, 5 and 6) and the presence of serum p53 in 100 individuals, 37 of whom has developed a haemopoietic malignancy during a 12-year follow-up of 39,000 Finnish adults. Serum p53 was detectable in six of the 63 (10%) matched controls and in 13/31 (42%) patients who developed a malignancy of lymphoid origin approximately 7 years after serum withdrawal. Six patients who developed a malignancy of myeloid origin were negative for p53. The presence of p53 alone was associated with a highly significant increased risk of lymphoid malignancies (relative risk (RR)p53 = 6.7, 95% confidence limits (CL) 1.9, 24) whereas high levels of antibody to EBNA2 seemed to be inversely related to the risk (RREBNA2 = 0.1, CL 0.0, 1.1). Among lymphoid malignancies, a combination of serum p53 and high EBNA1 antibody levels gave a greater than expected risk (RRp53 and EBNA1 = 14, CL 1.4, 130; RRexpected = 4.4), whereas interaction with high levels of EBNA5 antibody gave an expected risk (RRp53 and EBNA5 = 19, CL 1.7, 220; RRexpected = 17). Thus detectable levels of p53 appear early in the development of lymphoid malignancies, and high EBNA1 antibody levels, and accumulated p53 may both be synergistic risk indicators for lymphoid malignancies, whereas high EBNA5 antibody levels and accumulation of p53 seem to raise the RR independently of each other.

Flavonoid intake and coronary mortality in Finland: a cohort study.

OBJECTIVE: To study the association between dietary intake of flavonoids and subsequent coronary mortality. DESIGN: A cohort study based on data collected at the Finnish mobile clinic health examination survey from 1967-72 and followed up until 1992. SETTINGS: 30 communities from different parts of Finland. SUBJECTS: 5133 Finnish men and women aged 30-69 years and free from heart disease at baseline. MAIN OUTCOME MEASURE: Dietary intake of flavonoids, total mortality, and coronary mortality. RESULTS: In women a significant inverse gradient was observed between dietary intake of flavonoids and total and coronary mortality. The relative risks between highest and lowest quarters of flavonoid intake adjusted for age, smoking, serum cholesterol concentration, blood pressure, and body mass index were 0.69 (95% confidence interval 0.53 to 0.90) and 0.54 (0.33 to 0.87) for total and coronary mortality, respectively. The corresponding values for men were 0.76 (0.63 to 0.93) and 0.78 (0.56 to 1.08), respectively. Adjustment for intake of antioxidant vitamins and fatty acids weakened the associations for women; the relative risks for coronary heart disease were 0.73 (0.41 to 1.32) and 0.67 (0.44 to 1.00) in women and men, respectively. Intakes of onions and apples, the main dietary sources of flavonoids, presented similar associations. The relative risks for coronary mortality between highest and lowest quarters of apple intake were 0.57 (0.36 to 0.91) and 0.81 (0.61 to 1.09) for women and men, respectively. The corresponding values for onions were 0.50 (0.30 to 0.82) and 0.74 (0.53 to 1.02), respectively. CONCLUSIONS: The results suggest that people with very low intakes of flavonoids have higher risks of coronary disease.

CA 125 as a screening test for ovarian cancer.

BACKGROUND - Screening for ovarian cancer is based on ultrasound, colour Doppler, and tumour markers. There is only limited evidence on their discriminatory performance and no evidence on their effectiveness in reducing mortality. OBJECTIVE - To investigate the discriminatory performance of CA 125 as a screening test for ovarian cancer. METHODS - A registry of 15 093 serum samples drawn in 1968-72 was linked to the cancer registry. During follow up between 1968 and 1980 24 ovarian cancers were identified. One or two matched case-control design nested within the sample bank was applied and the concentrations of CA 125 were assessed. RESULTS - Case-control differences (relative risk 4-0, 95% confidence interval 1.0 to 15.5 at 20 kU/1) were found. Detection rate of the CA 125 test was 21-33% and the true negative rate was 75-98% depending on the cut off level and interval between drawing of the blood sample and diagnosis of the cancer. CONCLUSION - CA 125 is not a valid screening test if used alone. Case-control differences of borderline significance were found in CA 125 before diagnosis of ovarian cancer, but they were not large enough to provide a sufficient detection rate.

Rheumatoid factor, chronic arthritis and mortality.

OBJECTIVE: To investigate chronic arthritis and rheumatoid factor (RF) for their prediction of premature total and cardiovascular mortality. METHODS: In 1978-80, a representative population sample of 8000 Finns aged 30 or more was invited to participate in a comprehensive health examination; 90% complied. Arthritis was diagnosed on the basis of medical history, symptoms, and physical examination. Serum RF was determined by the sensitised sheep cell agglutination test. RESULTS: By the end of 1992 1597 of the subjects had died from all causes, including 876 deaths from cardiovascular diseases. When adjusted for age, gender and smoking, the relative risk of persons with RF positive arthritis dying from any cause was 1.61 (95% confidence interval (CI) 1.03 to 2.51); RF negative non-erosive arthritis was not associated with mortality (relative risk 1.03; 95% CI 0.72 to 1.49). In the absence of arthritis, 'false positive' RF titres > or = 128 predicted cardiovascular deaths with a relative risk of 1.74 (95% CI 1.06 to 2.86). CONCLUSION: Both RF positive arthritis and false positive RF reactions predict mortality, but through different disease patterns.

A longitudinal study of screening for endometrial cancer by endometrial biopsy in diabetic females.

Diabetics are at high risk of developing endometrial cancer; the relative risk of endometrial cancer in diabetics is fourfold in comparison to non-diabetic controls. The purpose of this longitudinal study was to evaluate the effectiveness of screening asymptomatic diabetic females in terms of the premalignant and malignant endometrial findings, and to try to determine the optimal screening interval. In 1980-1981, a group of 462 diabetic females was identified and registered. One half of them (237) was invited to be screened. Endometrial samples were taken by using Vabra aspiration. The results of this first randomized screening in 1980-1981 have been published elsewhere. At that time 124 females participated. The remaining 225 females acted as an unscreened control group. Eight years later (1988-1989), both groups were invited to be screened. The Pistolet aspiration method was used. At this stage, group 1 (screened in 1980-1981) consisted of 78 females, and group 2 (not screened in 1980-1981) consisted of 148 females. In 85% (193/226) of the females, the uterine cavity was reached with the Pistolet instrument; 96% of the females found the pain acceptable. In the group screened twice (group 1), no pathologic lesions of the endometrium were found in the second screening. In the group screened for the first time (group 2), one female had endometrial adenocarcinoma (0.8%), one had complex hyperplasia without atypia (0.8%) and four had endometrial polyps (3.3%). In 165 cases of 193, both a cytologic and a histologic specimen were available. In 130 cases (79%) the cytology was of class I, including the one endometrial adenocarcinoma. In three cases (2%) it was of class II and in one case (1%) of class III. Endometrial biopsy by Pistolet aspiration was a method highly acceptable by the patients for examining the endometrium. However, cytologic examination was not able to show the existing endometrial adenocarcinoma. One endometrial sampling of asymptomatic diabetic females during early menopause could detect the bulk of the occult, slowly progressing lesions of the endometrium. Such screeening might be most efficient in terms of cost-benefit ratio.

Poor applicability of the Friedewald formula in the assessment of serum LDL cholesterol for clinical purposes.

OBJECTIVE: To determine the accuracy of the estimation of serum low-density lipoprotein (LDL) cholesterol concentration by the Friedewald formula. METHODS: Modifications of the calculation formula are presented on the basis of ultracentrifugal separation of serum high-density lipoprotein and LDL cholesterol in the specimens collected (n = 1215) in a nationwide health survey. RESULTS: The formulas obtained from different subject groups differed relatively little from each other. The accuracy of the original Friedewald formula was poor; in about 36% of the subjects the error was more than 5% compared with ultracentrifugally obtained results. By applying the currently recommended coronary heart disease (CHD) risk categorizations, high proportions (5%-28%) of the subjects were classified into wrong CHD risk categories when LDL cholesterol was calculated with any of the formulas. At high serum triglyceride levels, misclassifications were especially common. CONCLUSIONS: We conclude that even the most accurate LDL cholesterol calculation methods should be used with caution while classifying subjects into categories of CHD risk. In hypertriglyceridemic subjects, the calculation formulas probably should not be used at all.

Antioxidant vitamins in the diet: relationships with other personal characteristics in Finland.

STUDY OBJECTIVE: The study aimed to reveal associations between dietary antioxidant vitamins and other personal characteristics. DESIGN: Population based, cross sectional survey. SETTING: Twenty seven rural, industrial, and semiurban communities in six different regions of Finland. PARTICIPANTS: Subjects included 5304 men and 4750 women aged 15 years or older, who were interviewed about their dietary habits at the baseline study of the Finnish Mobile Clinic Health Examination Survey, 1967-72. MAIN RESULTS: Intakes of carotenoids and vitamins A, E, and C were estimated from dietary history interviews covering the subjects' food consumption in the preceding year. In older age groups intakes of all the vitamins studied were low. Occupation had a profound effect on dietary antioxidant vitamins: intakes were highest in white collar workers and lowest in farmers; those classified as service workers, industrial workers, or housewives came in between. Current smoking was inversely associated with dietary carotenoids and vitamin C, especially in men. The vitamin intakes of ex-smokers were equal to or even slightly higher than those of never smokers. Married men had higher intakes of carotenoids and vitamin C than men living alone. Body mass index was not an important determinant of the intake of antioxidant vitamins. CONCLUSIONS: The associations of dietary antioxidant vitamins with sociodemographic characteristics and smoking were strong enough to exert a confounding or modifying effect in studies on diet and diseases.

Health-based reference values of the Mini-Finland Health Survey: 2. Cholesterol in total serum and in different lipoprotein fractions.

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 4.2-8.5 mmol l-1 for men, and 4.2-9.4, 4.1-8.6, and 4.2-9.0 mmol l-1 for women, respectively. The corresponding medians were 6.3, 6.2 and 6.2 mmol l-1 in men, and 6.4, 6.0 and 6.1 mmol l-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.

Health-based reference values of the Mini-Finland Health Survey: 3. Triglycerides in total serum and in different lipoprotein fractions.

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 l-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.(ABSTRACT TRUNCATED AT 250 WORDS)

The risk of endometrial cancer in diabetic and hypertensive patients: a nationwide record-linkage study in Finland.

The risk of endometrial cancer (EC) in diabetics and hypertensives was studied as part of the planning of a trial of the efficacy of screening for EC. Two nationwide registers, the Finnish Cancer Registry and the Social Insurance Institution's (SII) population register, were linked to obtain 1715 EC patients diagnosed during 1970-1974 with individually matched controls. Data on the right for state-reimbursed medication for diabetes or hypertension prior to the case's cancer diagnosis was obtained from the SII's population register and was used as indicator of the diseases in question. Diabetes was a strong and hypertension a relatively weak risk factor for EC. The relative risk for the association of EC with diabetes was 4.1 (95% confidence limits 2.7 and 6.9) and with hypertension 1.6 (95% confidence limits 1.3 and 2.1). Diabetics and hypertensives are identifiable risk groups for EC in Finland. Diabetics form a suitable target population for a trial of the efficacy of screening for EC.

Depression and cardiovascular diseases.

We first review the associations between depression and cardiovascular diseases (CVDs). Then we examine them in the nationally representative Mini-Finland Health Survey, which covers 8,000 persons. Chronic somatic diseases and mental disorders were diagnosed using standardized methods. Cross-sectionally, CVDs and neurotic depression were associated both before and after adjustment for covariates. The strongest associations were observed in the case of severe CVDs. During a 6.6 year follow-up, the risk of CVD death and coronary death was elevated in depressed persons both with and without CVDs at entry. Much of the cross-sectional association is probably due to depression caused by CVDs. The outcome of CVD may be poorer in depressed persons. The hypothesis that depression is a cause of CVDs requires further study.

Tumour markers and screening for gastrointestinal cancer: a follow up study in Finland.

BACKGROUND: Screening for gastrointestinal cancer is based mainly on a barium contrast x ray method and on identification of occult blood in stools. The methods are relatively expensive, not always acceptable to the participants, and there is only limited evidence of their effectiveness in reducing the mortality from gastrointestinal cancer. OBJECTIVE: To investigate the validity of several tumour markers as a screening test for stomach cancer and for colorectal cancer. METHODS: A registry of 36,265 serum samples drawn during 1968-72 was linked to the cancer registry. Follow up was during 1968-80 when 94 stomach cancers and 95 colorectal cancers were identified. One to two matched case-control design was applied, and the concentrations of CEA, CA 19-9, CA 50, and TATI were assessed. RESULTS: The mean values of the markers between the cases and the controls were almost the same for the total material. Case-control differences were found between the 11 sets with an interval of less than one year between drawing the sample and diagnosis of the cancer. The highest validity was found in CEA for colorectal cancer (specificity 91%; sensitivity 64%) and in CA 19-9 for stomach cancer (specificity 74%; sensitivity 73%). CONCLUSION: CEA, CA 19-9, CA 50, or TATI are not valid screening tests. Case-control differences were found with a potential one year screening interval, but they were not large enough for sufficient validity.

Musculoskeletal disorders as determinants of disability in Finns aged 30 years or more.

The relationship between disability and various musculoskeletal disorders was investigated in 7217 men and women representative of the Finnish population aged 30 years or more. They participated in the Mini-Finland Health Survey and were first screened by interview and questionnaire about limitations in daily activities. The outcome variables were reduced working capacity, an occasional need for assistance in daily activities, and a regular need for assistance in daily activities. In a two-phase medical examination, all cases fulfilling predetermined diagnostic criteria of musculoskeletal, cardiovascular, respiratory and mental disorders and diabetes were recorded independently. In multivariate logistic regression analyses, inflammatory arthritis was the strongest determinant of all forms of disability. Osteoarthritis, especially in the hip, was a strong determinant of both occasional and regular need for assistance, and chronic low back pain was a strong determinant of reduced working capacity and occasional need for assistance among those aged 30-64 years. Other musculoskeletal disorders also determined the prevalence disability, but these relationships were reduced by taking comorbidity into account. A low level of education and a low (less than 20 kg/m2) or very high (at least 35 kg/m2) body mass index represented independent determinants of all forms of disability, and a history of physically strenuous work an independent determinant of reduced working capacity, when disabling illness was adjusted for. The proportion of all forms of disability attributable to musculoskeletal disorders, in models including, age, sex, other disabling illness and significant non-medical determinants of disability, was close to 20%. The disorders with the highest community impact were chronic low back pain among those aged 30-64, osteoarthritis of the hips and knees and inflammatory arthritis.

Serum tumor markers CEA, CA 50, TATI, and NSE in lung cancer screening.

BACKGROUND: There are no effective means for screening for lung cancer, so the authors assessed the utility of four lung cancer tumor makers for screening. METHODS: A case-control study, nested in a cohort study based on the linkage of records of health survey examinees with Finnish Cancer Registry records, was used to test the validity of tumor markers carcinoembryonic antigen (CEA), tumor-associated trypsin inhibitor (TATI), neuron-specific enolase (NSE), and CA 50 in lung cancer screening. Ten years after health examinations, record linkage indicated that 187 men had lung cancer; 344 control subjects, matched for age, sex, and municipality were drawn from the same records. RESULTS: The data allowed assessment of the sensitivity of the marker assays at a 95% specificity level, which was highest for CEA (17% at a concentration level of 5.3 micrograms/l). Logistic discrimination analysis indicated that of the other markers, only TATI, when used in combination, improved the discriminatory power of CEA. CEA and TATI levels correlated significantly with smoking. They also showed a significant gradient toward increasing risk of lung cancer from the lowest to the highest quintiles of marker levels (for CEA, crude relative risk between the highest and lowest quintiles, 8.6). The gradient also was evident in the subgroup whose cancer had been diagnosed more than 5 years after serum specimen collection. The trend persisted, although relative risk was halved after adjustment for smoking. CONCLUSIONS: The markers do not seem to be useful tools for lung cancer screening. However, CEA and TATI levels seem to give information on cancer risk long before the clinical cancer stage, as the quintile-based analyses of marker levels indicate.