Persistent organochlorine pesticides in serum and risk of Parkinson disease.

BACKGROUND: Pesticides have been implicated as likely environmental risk factors for Parkinson disease (PD), but assessment of past exposure to pesticides can be difficult. No prior studies of pesticide exposure and PD used biomarkers of exposure collected before the onset of PD. Our investigation examined the association between prospective serum biomarkers of organochlorine pesticides and PD. METHODS: We conducted a nested case-control study within the Finnish Mobile Clinic Health Examination Survey, with serum samples collected during 1968-1972, and analyzed in 2005-2007 for organochlorine pesticides. Incident PD cases were identified through the Social Insurance Institution's nationwide registry and were confirmed by review of medical records (n = 101). Controls (n = 349) were matched for age, sex, municipality, and vital status. Adjusted odds ratios (ORs) of PD were estimated using logistic regression. RESULTS: Little association emerged with a summary score of the 5 organochlorine pesticides found at high levels, and only increasing dieldrin concentrations trended toward a higher risk of PD (OR per interquartile range [IQR] 1.28, 95% confidence interval [CI] 0.97-1.69, p = 0.08). Because of possible strong confounding by cigarette smoking among smokers, we ran additional analyses restricted to never smokers (n = 68 cases, 183 controls). In these analyses, increasing dieldrin concentrations were associated with increased odds of PD (OR per IQR 1.95, 95% CI 1.26-3.02, p = 0.003). None of the other organochlorine pesticides were associated with PD in these analyses. CONCLUSIONS: These results provide some support for an increased risk of Parkinson disease with exposure to dieldrin, but chance or exposure correlation with other less persistent pesticides could contribute to our findings.

Common candidate gene variants are associated with QT interval duration in the general population.

OBJECTIVES: QT interval prolongation is associated with increased risk of sudden cardiac death at the population level. As 30-40% of the QT-interval variability is heritable, we tested the association of common LQTS and NOS1AP gene variants with QT interval in a Finnish population-based sample. METHODS: We genotyped 12 common LQTS and NOS1AP genetic variants in Health 2000, an epidemiological sample of 5043 Finnish individuals, using Sequenom MALDI-TOF mass spectrometry. ECG parameters were measured from digital 12-lead ECGs and QT intervals were adjusted for age, gender and heart rate with a nomogram (Nc) method derived from the present study population. RESULTS: The KCNE1 D85N minor allele (frequency 1.4%) was associated with a 10.5 ms (SE 1.6) or 0.57 SD prolongation of the adjusted QT(Nc) interval (P=3.6 x 10(-11)) in gender-pooled analysis. In agreement with previous studies, we replicated the association with QT(Nc) interval with minor alleles of KCNH2 intronic SNP rs3807375 [1.6 ms (SE 0.4) or 0.08 SD, P=4.7 x 10(-5)], KCNH2 K897T [-2.6 ms (SE 0.5) or -0.14 SD, P=2.1 x 10(-7)] and NOSA1P variants including rs2880058 [4.0 ms (SE 0.4) or 0.22 SD, P=3.2 x 10(-24)] under additive models. CONCLUSIONS: We demonstrate that each additional copy of the KCNE1 D85N minor allele is associated with a considerable 10.5 ms prolongation of the age-, gender- and heart rate-adjusted QT interval and could thus modulate repolarization-related arrhythmia susceptibility at the population level. In addition, we robustly confirm the previous findings that three independent KCNH2 and NOSA1P variants are associated with adjusted QT interval.

Malignancies in cases with screening-identified evidence of coeliac disease: a long-term population-based cohort study.

BACKGROUND AND AIMS: The association between diagnosed coeliac disease and malignancy has been established. The present study was conducted to determine whether previously unrecognised and thus untreated adults with screening-identified evidence of coeliac disease carry an increased risk of malignancies. METHODS: A Finnish population-based adult-representative cohort of 8000 individuals was drawn in 1978-1980. Stored sera of the participants with no history of coeliac disease or any malignancy were tested for immunoglobulin A (IgA) class tissue transglutaminase antibodies (Eu-tTG) in 2001. Positive sera were further analysed by another tissue transglutaminase antibody test (Celikey tTG) and for endomysial antibodies (EMAs). Malignant diseases were extracted from the nationwide database and antibody-positive cases were compared with negative cases during a follow-up of nearly 20 years. RESULTS: Altogether 565 of all the 6849 analysed serum samples drawn in 1978-80 were Eu-tTG positive. In further analyses, 202 (2.9%) of the participants were Celikey tTG positive and 73 (1.1%) were EMA positive. The overall risk of malignancy was not increased among antibody-positive cases in the follow-up of two decades; the age- and sex-adjusted relative risk was 0.91 (95% CI 0.60 to 1.37) for those who were Celikey tTG positive and 0.67 (95% CI 0.28 to 1.61) for those who were EMA positive. CONCLUSIONS: The prognosis of adults with unrecognised coeliac disease with positive coeliac disease antibody status is good as regards the overall risk of malignancies. Thus, current diagnostic practice is sufficient and there is no need for earlier diagnosis of coeliac disease by mass screening on the basis of the findings of this study.

Prospective study of coffee consumption and risk of Parkinson's disease.

OBJECTIVE: To examine the prediction of coffee consumption on the incidence of Parkinson's disease. SUBJECTS AND METHODS: The study population comprised 6710 men and women, aged 50-79 years and free from Parkinson's disease at the baseline. At baseline, enquiries were made about coffee consumption in a self-administered questionnaire as the average number of cups per day. During a 22-year follow-up, 101 incident cases of Parkinson's disease occurred. Parkinson's disease cases were identified through a nationwide registry of patients receiving medication reimbursement, which is based on certificates from neurologist. RESULTS: After adjustments for age, sex, marital status, education, community density, alcohol consumption, leisure-time physical activity, smoking, body mass index, hypertension and serum cholesterol, the relative risk for subjects drinking 10 or more cups of coffee per day compared with non-drinkers was 0.26 (95% confidence interval 0.07-0.99, P-value for trend=0.18). The association was stronger among overweight persons and among persons with lower serum cholesterol level (P-value for interaction=0.04 and 0.03, respectively). CONCLUSIONS: The results support the hypothesis that coffee consumption reduces the risk of Parkinson's disease, but protective effect of coffee may vary by exposure to other factors.

Prediction of type 1 diabetes among siblings of affected children and in the general population.

AIMS/HYPOTHESIS: To compare the predictive characteristics of autoantibodies to GAD (GADA) and islet antigen 2 (IA-2A) for type 1 diabetes between siblings of affected children and children from the general population. METHODS: Seven-hundred and fifty-five siblings and 3,475 population-derived children were screened for GADA and IA-2A and observed for type 1 diabetes for 15 years. Sensitivity and cumulative disease risks from GADA, IA-2A and double positivity were compared between the cohorts. RESULTS: Fifty-six siblings (7.4%) tested positive for GADA, 39 (5.2%) for IA-2A and 29 (3.8%) for both autoantibodies. Thirty-four population derived participants (1.0%) had GADA, 22 (0.6%) had IA-2A and 7 (0.2%) had double positivity. Fifty-one siblings (6.8%) and 15 participants in the population cohort (0.4%) progressed to type 1 diabetes. The predictive sensitivity of GADA was 68% (95% CI 53-81%) among siblings and 50% (95% CI 23-77%) in the general population, while the corresponding values were 58 (95% CI 43-72%) and 43% (95% CI 18-71%) for IA-2A. Double-autoantibody positivity had a sensitivity of 48% (95% CI 34-63%) among siblings and 36% (95% CI 13-65%) in the population cohort. Cumulative disease risks from GADA, IA-2A and double positivity were, respectively, 61% (95% CI 48-74%), 74% (95% CI 61-88%) and 83% (95% CI 69-97%) among siblings compared with those of 24% (95% CI 9-38%), 32% (95% CI 12-51%) and 86% (95% CI 60-100%) in the general population. CONCLUSIONS/INTERPRETATION: There were no significant differences in the disease-predictive sensitivity of GADA and IA-2A positivity or their combination between siblings and the population cohort, whereas, for each antibody, positivity was associated with a higher cumulative disease risk among siblings. Double-antibody positivity conferred similar cumulative disease risk both among siblings and in the general population.

Oral health indicators poorly predict coronary heart disease deaths.

Several earlier studies have suggested that development of coronary heart disease (CHD) is causally related to oral infections. The aim of this study was to investigate the association between oral health indicators and CHD deaths. Out of a nationally representative sample, 6527 men and women aged 30-69 years participated in the health examination with a dental check. Detailed oral health data included caries, periodontal and dental plaque status, presence of remaining teeth, and various types of dentures. Over a mean 12-year follow-up, persons dying of CHD were older and more often smoked, had hypertension, hypercholesterolemia, diabetes, and only a basic education compared with other persons. In univariate analyses, several oral health indicators were associated with CHD deaths. Adjustment for the established CHD risk factors reduced all these associations to statistical non-significance. The associations between oral health indicators and CHD are mostly explained by confounding factors, particularly those relating to health behavior.

Enterovirus, mycoplasma and other infections as predictors for myocardial infarction.

OBJECTIVES: To study antibodies against five infectious agents for their prediction of major coronary events in men with and without evidence of coronary heart disease at baseline. DESIGN: A case-control study nested within a prospective population study. SUBJECTS: The study cases included 441 men 45-64 years old with nonfatal myocardial infarction or coronary death within a mean follow-up time of 10 years. A total of 165 men had already signs of heart disease at baseline, whilst 276 were apparently healthy at the beginning of the study. Two controls for each case were matched for age, heart disease status and place of residence. Antibodies against enterovirus, Mycoplasma pneumoniae, Chlamydia pneumoniae, cytomegalovirus and adenovirus were determined. RESULTS: Men without reported baseline heart disease, but not those with heart disease, showing the highest quartile of antibodies to enterovirus and mycoplasma or increased levels of immune complex-bound antibodies to chlamydia had a significantly higher risk of coronary events than men with lower level of antibodies. The increased risk demonstrated in men with high levels of antibodies to enterovirus and mycoplasma remained significant after adjustment for other antibodies, acute-phase reactant and conventional risk factors. Serological evidence of infection by multiple agents was also significantly associated with coronary events. CONCLUSIONS: Serological evidence for several infectious agents is associated with the risk of coronary heart disease, but only in men without baseline history of heart disease.

Hyperhomocystinemia: a risk factor or a consequence of coronary heart disease?

BACKGROUND: Mild hyperhomocystinemia has been suggested as an indicator of an increased risk of cardiovascular disease. OBJECTIVE: To examine whether serum homocysteine concentration is a predictor of coronary heart disease (CHD) events. METHODS: A case-control study, nested in a population-based cohort study was used. During a follow-up of 13 years, 166 major coronary events (death from CHD or nonfatal myocardial infarction) occurred in men with evidence of heart disease at baseline and 272 events in men without a history of heart disease. Two controls per case were selected by individual matching. RESULTS: Among men with known heart disease at baseline, the relative risk (95% confidence interval) of CHD events adjusted for age, smoking, hypertension, diabetes mellitus, serum cholesterol level, body mass index, and alcohol consumption was 2.23 (95% confidence interval, 1.03-4.85) in the highest serum homocysteine quintile compared with the lowest quintile. Among the men free of heart disease at baseline, the corresponding relative risk was 0.90 (95% confidence interval, 0.51-1.60). CONCLUSIONS: This prospective study does not support the hypothesis that a high concentration of serum homocysteine is a risk factor for coronary events in a population free of heart disease. However, it does suggest that mild hyperhomocystinemia predicts secondary coronary events in men with heart disease, possibly as a consequence of atherosclerotic changes.

Homocysteine and major coronary events: a prospective population study amongst women.

OBJECTIVES: To study serum homocysteine concentration for its prediction of major coronary heart disease events amongst women. DESIGN: A case-control study nested within a follow-up study. Subjects. A total of 74 and 75 major coronary events (coronary deaths or nonfatal myocardial infarction) which occurred in women with and without known heart disease, respectively, during a 13-year follow-up and two individually matched controls per case. Main outcome measure. Major coronary event. RESULTS: Amongst women with baseline heart disease, the relative risk (95% CI) of such events, adjusted for age, smoking, hypertension, diabetes, serum cholesterol and body mass index, was 3.32 (1.05-10.5) in the highest homocysteine quintile compared with the lowest quintile. Amongst women free of heart disease at baseline, the corresponding relative risk value was 0.77 (0.24-2.45). CONCLUSIONS: This prospective study support the hypothesis that homocysteine is a risk factor for coronary events in women with heart disease.

Coffee consumption, rheumatoid factor, and the risk of rheumatoid arthritis.

BACKGROUND: Recent epidemiological studies have suggested that smoking is a risk factor for rheumatoid factor (RF) positive rheumatoid arthritis (RA). Being overweight, high serum cholesterol, and dietary factors have in some studies been found to be associated with the risk of RA. No attention, however, has been paid to coffee consumption as a risk determinant, though it is a shared covariate of the alleged risk factors. OBJECTIVES: This study aimed at examining coffee consumption for its associations with RF positivity and with the risk of RA. METHODS: Coffee consumption was studied, firstly, for its association with RF (sensitised sheep cell agglutination titre >/=128) in a cross sectional survey of 6809 subjects with no clinical arthritis, and secondly, for its prediction of RA in a cohort of 18 981 men and women who had neither arthritis nor a history of it at the baseline examination in 1973-76. Up to late 1989, 126 subjects of the cohort study had developed RA, of whom, 89 were positive for RF by the time of diagnosis. RESULTS: In the cross sectional survey the number of cups of coffee drunk daily was directly proportional to the prevalence of RF positivity. Adjusted for age and sex this association was significant (p value for linear trend, 0.008), but after further adjustment for smoking the linear trend declined below significance (p=0.06). In the cohort study there was an association between coffee consumption and the risk of RF positive RA that was not due to age, sex, level of education, smoking, alcohol intake, body mass index, or serum cholesterol. After adjustment for these potential confounders the users of four or more cups a day still had a relative risk of 2.20 (95% confidence interval 1.13 to 4.27) for developing RF positive RA compared with those drinking less. Coffee consumption did not predict the development of RF negative RA. CONCLUSION: Coffee consumption may be a risk factor for RA, possibly through mechanisms contributing to the production of RF. This hypothesis remains to be tested in further studies.

Serum albumin and colorectal cancer risk.

OBJECTIVE: To study the relationship between serum albumin and colorectal cancer occurrence. DESIGN: A case-control study nested within a cohort followed from 1968 to 1991. SUBJECTS AND METHODS: The albumin concentration was determined from serum samples stored at -20 degrees C at baseline in 177 incident colorectal cancer cases and 288 controls matched for sex, age and study region. RESULTS: An elevated risk was present of cancer of the left, distal colon at high serum albumin concentrations. No significant association was observed for the right, proximal colon or the rectum. The relative risks of cancer of the distal and proximal colon among individuals in the highest and lowest quartiles of serum albumin were 17.03 (95% confidence interval 1.48-195) and 0.77 (95% confidence interval 0. 19-3.13), respectively. CONCLUSIONS: The present study lends support to the hypothesis that some dietary factor associated with serum albumin may be a risk factor for distal colon cancer.

Airway obstruction in relation to symptoms in chronic respiratory disease--a nationally representative population study.

We examined the severity of airway obstruction and the occurrence of respiratory symptoms in a large, nationally representative population sample and in a subgroup of subjects with chronic bronchitis and/or emphysema to obtain information for developing national prevention and treatment strategies for these diseases. The study population comprised of 7217 randomly selected subjects (aged 30 years and older) who participated in a comprehensive health examination survey. The 'cases' were subjects diagnosed as having chronic bronchitis and/or emphysema. The survey methods comprised of questionnaires, interviews, physical measurements, including spirometry, and clinical examinations. In the whole study population, the age-adjusted prevalence of chronic bronchitis and/or emphysema was 22% among men and 7% among women, whilst clinically relevant airways obstruction (FEV1/FVC%< or = 69) was present in 11% of men and in 5% of women. The occurrence of chronic cough and phlegm production was lowest among the 'cases' with pronounced obstruction (in 68% of men with severe and in 60% of women with moderate obstruction), whereas cold air-associated dyspnoea aggravation showed an inverse relationship, occurring most commonly in men (80%) with severe obstruction. Unexpectedly, half of the bronchitic women had never smoked. We conclude that the occurrence of certain bronchitic symptoms, such as chronic cough and phlegm production and cold air-associated dyspnoea aggravation, may to some degree indicate different stages of the disease. Smoking was not closely associated with airflow limitation in women here.

Quercetin intake and the incidence of cerebrovascular disease.

OBJECTIVE: To study the relation between intake of the antioxidant flavonoid quercetin and subsequent incidence of cerebrovascular disease (CVA). DESIGN: A cohort study carried out among 9208 Finnish men and women 15 y or more of age and initially free from cardiovascular disease. During a 28 y follow-up period in 1967-1994, a total of 824 cases with CVA were diagnosed. METHODS: Food consumption data were collected using a dietary history interview method covering the total habitual diet during the previous year. RESULTS: Quercetin intake was not associated with CVA incidence. The relative risk of CVA adjusted for age, serum cholesterol, body mass index, smoking, hypertension, diabetes, geographical area, occupation and intake of beta-carotene, vitamin E, vitamin C, fibre, various fatty acids, and energy between the highest and lowest quartiles of quercetin intake was 0.99 (95% confidence interval (CI)=0.71-1.38) for men and 0.85 (CI=0.60-1.21) for women. In contrast, apples, the major source of quercetin in the study population, showed a significant inverse association both in men and women, mainly due to an association with thrombotic or embolic stroke. The relative risks of thrombotic stroke after further adjustment for quercetin intake were 0.59 (CI=0.35-0.99; P=0.45) and 0.61 (CI=0.33-1.12: P for trend=0.02) for men and women, respectively. CONCLUSIONS: The results suggest that the intake of apples is related to a decreased risk of thrombotic stroke. This association apparently is not due to the presence of the antioxidant flavonoid quercetin.

Dietary and other non-pharmacological treatments in patients with drug-treated hypertension and control subjects.

OBJECTIVE: To study the nutrient intakes and other lifestyle patterns of drug-treated hypertensives and control subjects. DESIGN: A cross-sectional population-based epidemiological study. SETTING: The participating study subjects visited the research laboratory of the Department of Internal Medicine of the University of Oulu, Oulu, Finland. PARTICIPANTS: A total of 1045 Finnish men and women aged 40-60 years, of whom 716 (69%) completed 7-day food records. MAIN OUTCOME MEASURES: Intakes of energy, protein, total fat, saturated, monounsaturated and polyunsaturated fatty acids, carbohydrate, alcohol, fibre, calcium, magnesium, potassium and sodium were assessed from 7-day food records. The study also included measurements of blood pressure, blood glucose and plasma lipids, and anthropometric variables. Information about alcohol consumption, smoking habits and physical activity was collected by interviewing. RESULTS: Obesity was common amongst the hypertensive subjects, whose body mass indices were significantly higher than those of the control subjects. Only minor differences existed in the energy intake levels and nutrient intakes of the hypertensive and control cohorts, but the control subjects performed more physical activity than the hypertensive subjects. The dietary recommendations concerning the intakes of total and saturated fats, carbohydrate and fibre were poorly met by both the hypertensive and the control subjects. Alcohol consumption was high amongst the hypertensive men, especially amongst the smokers. CONCLUSIONS: Non-pharmacological treatment, including dietary management, of hypertensive patients at high risk for cardiovascular complications seems still to be inadequate. Additional well-focused efforts are needed to intensify the dietary treatment as well as to reduce alcohol consumption and smoking amongst hypertensives.

Heart rate and mortality.

OBJECTIVES: Increased heart rate has shown to be associated with risk of mortality from cardiovascular diseases in some studies, but not in others. Increased heart rate has also been linked to causes of death other than cardiovascular. To clarify the role of heart rate as a predictor of death we studied its predictive value in a large population study. DESIGN: A prospective population study with a follow-up time of 23 years. SUBJECTS AND METHODS: The study population comprised 5598 men and 5119 women 30-59 years of age on entry. Heart rate was measured from resting ECGs. MAIN OUTCOME MEASURE: Mortality from specified causes. RESULTS: A total of 1848 men and 840 women died during the follow-up period. Increased heart rate was significantly associated with death from all causes, cardiovascular causes, and natural noncardiovascular, nonmalignant causes of death. Increased heart rate was associated with death from cancer in men with heart disease but not in men without heart disease on entry into the study. The increase in cardiovascular mortality with high heart rate was explained by the close association between heart rate and blood pressure. Adjustment for risk factors did not alter the significance of the association between increased heart rate and mortality from noncardiovascular causes. CONCLUSIONS: High heart rate is simple to observe clinically and a significant if nonspecific predictor of mortality. Increased risk of mortality from cardiovascular diseases can be explained by association with high blood pressure. The increased mortality risk associated with high heart rate related mainly to a group of diseases of noncardiovascular or nonmalignant origin.

N-acetyltransferase-2 polymorphism, smoking and type 1 diabetic nephropathy.

The N-acetyltransferase (NAT2) polymorphism has been suggested to be related to diabetic microvascular complications. To study the distribution of NAT2 genotypes in Caucasian type 1 diabetic patients with and without diabetic nephropathy, 214 adult type 1 diabetic patients and 53 healthy individuals were genotyped by polymerase chain reaction-restriction fragment length polymorphism. In addition, 75 young type 1 diabetic patients were genotyped, and 70 of them also phenotyped by caffeine. Of the adult patients, 83 had normal albumin excretion, 58 had microalbuminuria, and 73 had overt diabetic nephropathy. NAT2 allele frequencies were similarly distributed between the diabetic patients and healthy individuals: 0.29/0.2 5 (NAT2*4), 0.03/0.04 (NAT2*7B), 0.25/0.27 (NAT2*6A), and 0.43/0.44 (NAT2*5B), and within the diabetic subgroups. Because smoking is a known risk factor for diabetic nephropathy, nonsmoking and smoking patients were analysed separately. NAT2 allele frequencies differed significantly between the nonsmoking normoalbuminuric, microalbuminuric and nephropathic patients: 0.18/0.41/0.30 (NAT2*4), 0.04/0.00/0.02 (NAT2*7B), 0.35/0.18/0.17 (NAT2*6A), 0.43/0.41/0.50 (NAT2*5B), P = 0.013. In nonsmoking fast acetylators odds ratio for microalbuminuria and nephropathy was 3.1 (95% confidence interval 1.36-7.05), P = 0.007 by logistic regression. In smokers, a nonsignificant odds ratio was found [0.31 (95% confidence interval 0.08-1.2), P = 0.09]. Smoking is a strong confounding factor in relation to NAT2 analyses and diabetic nephropathy. According to our data, in nonsmoking type 1 diabetic patients fast NAT2 genotype implies an increased risk for diabetic nephropathy.

Serum testosterone and sex hormone-binding globulin concentrations and the risk of prostate carcinoma: a longitudinal study.

BACKGROUND: It has been hypothesized that high androgen levels are determinants of prostate carcinoma. METHODS: Serum concentrations of testosterone, sex hormone-binding globulin (SHBG), and androstenedione were analyzed to determine their role as predictors of prostate carcinoma in a longitudinal, population-based, nested case-control study. The serum concentrations of testosterone, SHBG, and androstenedione were determined from serum samples collected by the Finnish Mobile Clinic Health Examination Survey between 1968-1972 and stored at -20 degrees C. During a follow-up period of 24 years, a total of 166 prostate carcinoma cases occurred among men who originally were cancer free. Two controls (matched for age and municipality) were chosen. RESULTS: There was no association between serum testosterone, SHBG, or androstenedione concentrations and the occurrence of subsequent prostate carcinoma in the total study population or in subgroups determined based on age or body mass index. The association was not strengthened by simultaneous adjustment for the hormonal variables. CONCLUSIONS: The results of the current study do not appear to corroborate the hypothesis that serum testosterone, SHBG, or androstenedione are determinants of the subsequent occurrence of prostate carcinoma.

The survival and well-being of patients treated for Cushing's syndrome.

OBJECTIVE: The main aim of the study was to evaluate the survival, well-being and working capacity of patients treated for Cushing's syndrome. DESIGN: The study was carried out by retrospectively analysing patient records from years 1981-94. Follow-up time was extended from the time of diagnosis to the end of 1996. A questionnaire dealing with symptoms prior to and after therapy, and the quality of life estimated on a Visual Analogue Scale (VAS) was sent to all surviving patients. SETTING: The study was performed in a university hospital. MAIN OUTCOME MEASURES: Survival, subjective well-being, working capacity before and after treatment and disappearance of symptoms after treatment of Cushing's syndrome. RESULTS: During the follow-up time 10 patients died out of a total of 74. The overall standardized mortality ratio (SMR) was 168% (95% CI 81-309%). The SMR of patients with pituitary disease was 267% (89-525%), and in patients with adrenal adenoma it was 135% (16-489%). Forty-six per cent of the surviving patients stated that they felt fully recovered from the disease, but the proportion of patients having persisting symptoms after treatment was also noteworthy. The mean VAS score (range 0-100) was 19 (SD 14) before treatment and 82 (SD 18) after treatment (P<0.001). After treatment, 81% of the patients were able to return to work, 11% retired because of disability, 5% retired because of age and 3% were on sick-leave at the time of answering the questionnaire. During the follow-up time, 42% of the patients with pituitary disease suffered a relapse. However, the effect of the relapse on well-being was not significant. CONCLUSIONS: The mortality risk of patients treated for Cushing's disease was not significantly increased compared with that of the general population. Many symptoms persisted even years after therapy. After clinical recovery, working ability was not always regained.

Prevalence of the metabolic syndrome in drug-treated hypertensive patients and control subjects.

OBJECTIVES: To determine the prevalence of the metabolic abnormalities associated with hypertension and to define the predictors of the metabolic syndrome by different definitions in random population-based samples. DESIGN: A cross-sectional epidemiological study of hypertensive patients and controls. SETTING: The participating study subjects visited the research laboratory of the Department of Internal Medicine, University of Oulu, Oulu, Finland. SUBJECTS: Six hundred treated male and female hypertensives aged 40-59 years and 600 age- and sex-matched controls were randomly selected by age stratification from population registers. MAIN OUTCOME MEASURES: A wide range of laboratory analyses were conducted. After fasting blood had been drawn, the subjects were given a 75 g glucose load except previously known insulin-treated diabetics. Both 1 h and 2 h glucose and insulin concentrations were determined. During the same visit, a standardized health questionnaire covering the past medical history, current and former medication use, physical activity, smoking habits, alcohol consumption and family history was completed. Ten different definitions of the metabolic syndrome were applied to achieve a wide perspective of the prevalence of the different combinations. RESULTS: The prevalence of the metabolic syndrome in different samples varied depending on the definition from 0.8 to 35.3%, being lowest in the control men and women and highest in the hypertensive men. Three-quarters of a random, middle-aged, urban population show at least one cardiovascular risk factor and 91.3% of all the hypertensive subjects show at least one cardiovascular risk factor in addition to hypertension itself. The independent predictors of the metabolic syndrome were waist circumference, uric acid, total cholesterol and gamma-glutamyl transpeptidase in logistic analysis after adjustment for age, measure of obesity and gender. CONCLUSIONS: This cross-sectional, epidemiological study shows that the magnitude of the prevalence rates of the metabolic syndrome is at the same level in various populations, being less than one-third in population-based samples in spite of the different definitions. The cluster of several cardiovascular risk factors, especially in the hypertensives, leads to an increased relative risk of cardiovascular diseases.