[show abstract][hide abstract] ABSTRACT: Cardiovascular disease (CVD) event rates are decreasing, but the prevalence of diabetes is increasing. The effect of these developments on the population attributable fraction (PAF) of CVD events due to diabetes is not known.
We used country-wide healthcare registers to identify all persons aged 25-80 years treated for diabetes in Finland during 1992-2002. These data were further linked to the National Cardiovascular Disease Register to identify the first CVD events (acute coronary syndrome and ischaemic stroke) among the individuals with and without diabetes. We calculated the annual PAF of the first CVD events due to diabetes separately for men and women.
The number of men treated for diabetes each year almost doubled during the study period from 37,073 to 69,158 between 1992 and 2002. Among women, the number increased from 42,485 to 57,372. The annual number of first CVD events in the country declined among men with diabetes from 13,436 to 12,678 and among women with diabetes from 8,658 to 7,521 between 1992 and 2002. During the same period, the PAF due to diabetes of the first CVD events increased among men from 11.4% (95% CI 10.8, 12.0%) to 13.8% (95% CI 13.2, 14.5%) and decreased among women from 20.1% (95% CI 19.2, 21.0%) to 16.9% (95% CI 15.9, 17.8%). The trends in PAF were different between the sexes (p < 0.001 for the interaction year × sex).
Despite the very large increase in the prevalence of diabetes, the PAF of the first CVD events due to diabetes decreased in women and increased only slightly in men.
[show abstract][hide abstract] ABSTRACT: The study aimed to examine the role of the metabolic syndrome (MetS) as a predictor of incident cardiovascular disease (CVD) events and incident diabetes, and to compare the various definitions of MetS.
The population-based Health 2000 Study included 6105 individuals, aged 30-79 years, followed-up for 7 years. CVD during follow-up was defined as coronary death, acute myocardial infarction, coronary revascularization or stroke. MetS was defined according to the International Diabetes Federation (IDF), the 2005 National Cholesterol Education Program-Adult Treatment Panel III (ATP III), the World Health Organization (WHO) and the new Harmonization definitions. The Bayesian information criterion (BIC) was used to compare different Cox proportional-hazards regression models.
The highest prevalence estimates of MetS at baseline were observed with the Harmonization definition: 47.8% in men and 40.7% in women. During the follow-up, 238 cases of incident CVD and 172 cases of incident diabetes were observed. All definitions of MetS were significant predictors for incident CVD and diabetes. BIC suggested that the new Harmonization definition of MetS as one entity was a better predictor of the CVD endpoint than the sum of its components, but not for diabetes. Also, the Harmonization definition of MetS was a better predictor of CVD than the Framingham equation in women, but not in men.
Irrespective of definition, MetS is a significant predictor of incident CVD events and incident diabetes. Also, the new Harmonization definition may be a better predictor of incident CVD than the sum of its components.
[show abstract][hide abstract] ABSTRACT: The international Trial to Reduce IDDM in the Genetically at Risk (TRIGR) was launched to determine whether weaning to a highly hydrolysed formula in infancy reduces the incidence of type 1 diabetes in children at increased genetic disease susceptibility. We describe here the findings on feasibility and compliance from the pilot study.
The protocol was tested in 240 children. The diet of the participating children was assessed by self-administered dietary forms, a structured questionnaire and a food record. Blood samples were taken and weight and height measured at birth and at 3, 6, 9, 12, 18 and 24 months.
A majority of the subjects (84%) were exposed to the study formula at least for 2 months. Linear growth or weight gain over the first 2 years of life was similar in the two study groups. The levels of IgA and IgG antibodies to cow's milk and casein were higher in the cow's milk-based formula group than in the hydrolysed formula group during the intervention period (p<0.05), reflecting the difference in the intake of cow's milk protein.
This randomized trial on infant feeding turned out to be feasible, and dietary compliance was acceptable. Valuable experience was gained for the planning and sample size estimation of the study proper.
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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.
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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.
Journal of Internal Medicine 11/2008; 265(4):448-58. · 6.46 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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.
[show abstract][hide abstract] ABSTRACT: Geographical variations in the HLA-DQ genotypes associated with risk for type 1 diabetes were evaluated in Finland. Samples of 280 diabetic children diagnosed in Turku (south-west of the country) and 405 in Oulu (north of the country) were studied as well as a series of 14 096 and 10 016 newborns collected from the same hospitals. There were no major differences in the risk or protection conferred by various HLA-DQB1 genotypes between south-western and northern parts of the country when genotypes of children with type 1 diabetes from these two centres were compared with those of newborns, representing the background populations. However, the distribution of various genotypes was different, both in diabetic children and in newborns, when compared between the two regions (P < 0.0001, χ2 test). These differences reflected the allele frequencies in newborn cohorts in which HLA-DQB1*02 and DQB1*0301 were found more often in Turku and DQB1*0302 more often in Oulu (P < 0.0001 for all differences). Similar types of differences were detected when children who were diagnosed as having diabetes during the national ‘Childhood Diabetes in Finland’ (DiMe) study between the years 1986–1989 were compared according to their residence. The observed differences in genotype and allele frequencies demonstrate the heterogeneity for HLA alleles even in a population that is generally regarded as highly homogeneous. These differences also affect the sensitivity and efficiency of the screening programme used for identifying infants with genetic susceptibility to IDDM in the ongoing Finnish Diabetes Prediction and Prevention Study.
European Journal of Immunogenetics 10/2008; 27(4):225 - 230.
[show abstract][hide abstract] ABSTRACT: To examine the prediction of coffee consumption on the incidence of Parkinson's disease.
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.
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).
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.
European Journal of Clinical Nutrition 08/2008; 62(7):908-15. · 2.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: Indoleamine 2,3-dioxygenase (IDO) is an important immunomodulator suppressing the activation of T lymphocytes, and its level in blood is increased in several autoimmune and inflammatory diseases. We have previously shown that this activity associates with several signs and risk factors of atherosclerosis in 24 to 39-year-old females. Now we repeat this analysis in an older population (n = 921, age range 46-76 years), i.e. in a population with more advanced atherosclerosis. IDO activity had a significant positive correlation in both sexes with carotid artery intima/media thickness (IMT), an early marker of atherosclerosis. In females, a significant negative correlation with HDL cholesterol and a positive correlation with triglycerides levels was observed. The association with IMT did not remain significant after adjustment with classical risk factors of atherosclerosis. It is thus concluded that IDO is a sensitive marker of atherosclerosis--or the inflammatory response associated with it--but does not have an independent role in the pathogenesis of this disease.
Scandinavian journal of clinical and laboratory investigation 08/2008; 68(8):767-70. · 1.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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.
[show abstract][hide abstract] ABSTRACT: The number of coeliac disease diagnoses has increased in the recent past and according to screening studies, the total prevalence of the disorder is around 1%.
To establish whether the increased number of coeliac disease cases reflects a true rise in disease frequency.
The total prevalence of coeliac disease was determined in two population-based samples representing the Finnish adult population in 1978-80 and 2000-01 and comprising 8000 and 8028 individuals, respectively. Both clinically-diagnosed coeliac disease patients and previously unrecognized cases identified by serum endomysial antibodies were taken into account.
Only two (clinical prevalence of 0.03%) patients had been diagnosed on clinical grounds in 1978-80, in contrast to 32 (0.52%) in 2000-01. The prevalence of earlier unrecognized cases increased statistically significantly from 1.03% to 1.47% during the same period. This yields a total prevalence of coeliac disease of 1.05% in 1978-80 and 1.99% in 2000-01.
The total prevalence of coeliac disease seems to have doubled in Finland during the last two decades, and the increase cannot be attributed to the better detection rate. The environmental factors responsible for the increasing prevalence of the disorder are issues for further studies.
[show abstract][hide abstract] ABSTRACT: Electrocardiographic evidence of left ventricular hypertrophy (ECG-LVH) has a grave prognostic significance in hypertensive patients. The purpose of our study was to assess whether ECG-LVH is more strongly associated with home-measured blood pressure (BP) than with clinic BP, and whether the correlation between home BP and ECG-LVH increases with the number of home measurements performed. We studied a representative sample of the general adult population (1989 subjects 45-74 years of age) in Finland. Subjects included in the study underwent a clinical interview, electrocardiography and measurement of clinic BP (mean of two clinic measurements) and home BP (mean of 14 duplicate home measurements performed during 1 week). Home BP correlated significantly better than clinic BP with the Sokolow-Lyon voltage (home/clinic systolic: r=0.23/0.22, P=0.60; diastolic: r=0.17/0.12, P=0.009), Cornell voltage (systolic: r=0.30/0.25, P=0.004; diastolic: r=0.21/0.12, P<0.001) and Cornell product (systolic: r=0.30/0.24, P=0.001; diastolic r=0.22/0.14, P<0.001) criteria of ECG-LVH. The correlation between home BP and ECG-LVH increased slightly with the number of home measurements, but even the mean of the initial two home BP measurements correlated equally well (systolic BP), or better (diastolic BP) with ECG-LVH than did clinic BP. In conclusion, home BP measurement allows us to obtain a large number of measurements that have a strong association with ECG-LVH. Our data support the application of home BP measurement in clinical practice.
Journal of Human Hypertension 11/2007; 21(10):788-94. · 2.82 Impact Factor
[show abstract][hide abstract] ABSTRACT: Short-QT syndrome is an inherited disorder characterized by a short QT interval and an increased risk of sudden cardiac death. The clinical significance of a short QT interval observed in a randomly recorded ECG is not known. Therefore, we assessed the prevalence and prognostic significance of a short QT interval in a general population.
QT intervals were measured from the 12-lead ECGs of 10 822 randomly selected middle-aged subjects (5658 males, mean age 44+/-8.4 years) enrolled in a population study and followed up for 29+/-10 years. The end points were all-cause and cardiovascular mortality. In addition to Bazett's method (corrected QT interval, or QTc), the Fridericia (QTfc) and nomogram (QTnc) methods were used to correct the QT interval for heart rate. The cutoff values for short QT intervals were defined as 320 ms (very short) and 340 ms (short). The prevalence of QT interval <320 ms based on QTc, QTfc, and QTnc was 0.10%, 0.08%, and 0.06%, and the prevalence of QT interval <340 ms was 0.4%, 0.3%, and 0.3%, respectively. The majority of subjects with short QT intervals were males. All-cause or cardiovascular mortality did not differ between subjects with a very short or short QT interval and those with normal QT intervals (360 to 450 ms). There were no sudden cardiac deaths, aborted sudden cardiac deaths, or documented ventricular tachyarrhythmias among subjects with a QTfc <340 ms.
A short QT interval does not appear to indicate an increased risk for all-cause or cardiovascular mortality in middle-aged nonreferral, community-based individuals.
[show abstract][hide abstract] ABSTRACT: The stiffening of arteries is associated with various cardiovascular diseases. Arterial stiffening can be studied utilizing arterial pulse wave velocity (PWV), but the absence of reliable reference values for PWV has limited its use in clinical practice. The aim of this study was to establish a range of reference values for PWV. PWV was examined by measuring the time difference of systolic pulse waves in arteries from the aortic arch to the popliteal artery using whole-body impedance cardiography (ICG). The study population consisted of 799 individuals (age range 25-76 years), 283 of whom had no evidence of cardiovascular disease, and a low burden of risk factors was selected to represent an apparently healthy population. In healthy study population, PWV was higher in males (8 x 9 +/- 1 x 8 m s(-1)) than females (8 x 1 +/- 2 x 0 m s(-1), P<0 x 001). Young males had lower PWV values than old males. Correspondingly, young females also had lower PWV values than old females. PWV was clearly associated with age, and PWV was higher in young and middle-aged males than in females. There was no statistically significant difference between old males and females in PWV. In conclusion, whole-body ICG provides a practical method for PWV measurement. Reference values can be useful in the clinical management of patients, especially in detecting early vascular disease or an increased risk of cardiovascular complications.
[show abstract][hide abstract] ABSTRACT: The aim of this study was to investigate whether the use of antimicrobials is associated with the risk of childhood type 1 diabetes.
The study population included all children born in Finland between 1996 and 2000 who were diagnosed with type 1 diabetes by the end of 2002. For each case (n=437), four matched controls were selected. Data on diabetes and the maternal use of antimicrobials was derived from nationwide registries.
Maternal use of phenoxymethyl penicillins (odds ratio [OR]=1.70, 95% CI 1.08-2.68, p=0.022) or quinolone antimicrobials (OR=2.43, 95% CI 1.16-5.10, p=0.019) before pregnancy was associated with an increased risk of type 1 diabetes in the child, whereas the use of other specific antimicrobials was not related to the risk. The risk was also higher among mother-child pairs where macrolides were used both by the mother before pregnancy and by the child, compared with pairs where neither used macrolides (OR=1.76, 95% CI 1.05-2.94, p=0.032). Maternal use of antimicrobials during pregnancy was not associated with an increased risk. The high use of antimicrobials by the child (more than seven vs seven or less purchases) was related to greater risk (OR=1.66, 95% CI 1.24-2.24, p=0.001).
Overall, the use of antimicrobials before pregnancy, during pregnancy or during childhood was not related to the risk of childhood type 1 diabetes. However, the use of some specific antimicrobials by the mother before pregnancy and by the child may be associated with an increased risk. Further studies are needed to confirm these associations and to elucidate the underlying mechanisms of action.
[show abstract][hide abstract] ABSTRACT: End-stage renal disease (ESRD) is one of the most severe complications of type 1 diabetes. Yet, data on patients' risk of developing ESRD are sparse.
To estimate the long-term risk of developing ESRD and to assess how age at diagnosis of diabetes, time period of diagnosis, and sex affect the risk.
A cohort of all patients younger than 30 years diagnosed as having type 1 diabetes in Finland in 1965-1999 (n = 20,005) was identified from the Finnish Diabetes Register. The cohort was followed up from diagnosis of diabetes until development of ESRD (dialysis or kidney transplantation as identified from the Finnish Registry for Kidney Diseases), death, or end of follow-up on December 31, 2001.
Cumulative incidence of ESRD, accounting for death as a competing risk.
The cohort was followed up for maximally 37 years, with a median of 16.7 years. During 346 851 person-years, 632 patients developed ESRD. The cumulative incidence of ESRD was 2.2% at 20 years and 7.8% at 30 years after diagnosis. The risk of developing ESRD was lowest in patients whose diagnosis occurred at younger than 5 years. The risk of ESRD was lower for patients diagnosed as having type 1 diabetes in later years. The risk did not differ significantly between sexes.
With regard to ESRD, the prognosis of type 1 diabetes has improved during the past 4 decades. Children diagnosed as having diabetes before age 5 years have the most favorable prognosis. Overall, incidence of ESRD appears to be lower than previously estimated.
JAMA The Journal of the American Medical Association 11/2005; 294(14):1782-7. · 29.98 Impact Factor