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BackgroundExperimental and clinical evidence implicates testosterone in the aetiology of prostate cancer. Variation across the normal range of circulating free testosterone concentrations may not lead to changes in prostate biology, unless circulating concentrations are low. This may also apply to prostate cancer risk, but this has not been investigated in an epidemiological setting.ObjectiveTo examine whether men with low concentrations of circulating free testosterone have a reduced risk of prostate cancer.Design, setting, and participantsAnalysis of individual participant data from 20 prospective studies including 6933 prostate cancer cases, diagnosed on average 6.8 yr after blood collection, and 12 088 controls in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group.Outcome measurements and statistical analysisOdds ratios (ORs) of incident overall prostate cancer and subtypes by stage and grade, using conditional logistic regression, based on study-specific tenths of calculated free testosterone concentration.Results and limitationsMen in the lowest tenth of free testosterone concentration had a lower risk of overall prostate cancer (OR=0.77, 95% confidence interval [CI] 0.69-0.86; p

BackgroundRegular fish and omega-3 consumption may have several health benefits and are recommended by major dietary guidelines. Yet, their intakes remain remarkably variable both within and across populations, which could partly owe to genetic influences.ObjectiveTo identify common genetic variants that influence fish and dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) consumption.DesignWe conducted genome-wide association (GWA) meta-analysis of fish (n = 86,467) and EPA+DHA (n = 62,265) consumption in 17 cohorts of European descent from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium Nutrition Working Group. Results from cohort-specific GWA analyses (additive model) for fish and EPA+DHA consumption were adjusted for age, sex, energy intake, and population stratification, and meta-analyzed separately using fixed-effect meta-analysis with inverse variance weights (METAL software). Additionally, heritability was estimated in 2 cohorts.ResultsHeritability estimates for fish and EPA+DHA consumption ranged from 0.13-0.24 and 0.12-0.22, respectively. A significant GWA for fish intake was observed for rs9502823 on chromosome 6: each copy of the minor allele (FreqA = 0.015) was associated with 0.029 servings/day (~1 serving/month) lower fish consumption (P = 1.96x10-8). No significant association was observed for EPA+DHA, although rs7206790 in the obesity-associated FTO gene was among top hits (P = 8.18x10-7). Post-hoc calculations demonstrated 95% statistical power to detect a genetic variant associated with effect size of 0.05% for fish and 0.08% for EPA+DHA.ConclusionsThese novel findings suggest that non-genetic personal and environmental factors are principal determinants of the remarkable variation in fish consumption, representing modifiable targets for increasing intakes among all individuals. Genes underlying the signal at rs72838923 and mechanisms for the association warrant further investigation.

Background: QRS duration and corrected QT (QTc) interval have been associated with sudden cardiac death (SCD), but no data are available on the significance of repolarization component (JTc interval) of the QTc interval as an independent risk marker in the general population.Objective: In this study, we sought to quantify the risk of SCD associated with QRS, QTc, and JTc intervals.Methods: This study was conducted using data from 3 population cohorts from different eras, comprising a total of 20,058 individuals. The follow-up period was limited to 10 years and age at baseline to 30-61 years. QRS duration and QT interval (Bazett's) were measured from standard 12-lead electrocardiograms at baseline. JTc interval was defined as QTc interval - QRS duration. Cox proportional hazards models that controlled for confounding clinical factors identified at baseline were used to estimate the relative risk of SCD.Results: During a mean period of 9.7 years, 207 SCDs occurred (1.1 per 1000 person-years). QRS duration was associated with a significantly increased risk of SCD in each cohort (pooled hazard ratio [HR] 1.030 per 1-ms increase; 95% confidence interval [CI] 1.017-1.043). The QTc interval had borderline to significant associations with SCD and varied among cohorts (pooled HR 1.007; 95% CI 1.001-1.012). JTc interval as a continuous variable was not associated with SCD (pooled HR 1.001; 95% CI 0.996-1.007).Conclusion: Prolonged QRS durations and QTc intervals are associated with an increased risk of SCD. However, when the QTc interval is deconstructed into QRS and JTc intervals, the repolarization component (JTc) appears to have no independent prognostic value. [ABSTRACT FROM AUTHOR]

Background: Poor R-wave progression (PRWP) is a common clinical finding on the standard 12-lead electrocardiogram (ECG), but its prognostic significance is unclear.Objective: The purpose of this study was to examine the prognosis associated with PRWP in terms of sudden cardiac death (SCD), cardiac death, and all-cause mortality in general population subjects with and without coronary artery disease (CAD).Methods: Data and 12-lead ECGs were collected from a Finnish general population health examination survey conducted during 1978-1980 with follow-up until 2011. The study population consisted of 6854 subjects. Main end points were SCD, cardiac death, and all-cause mortality. PRWP was defined as R-wave amplitude ≤ 0.3 mV in lead V3 and R-wave amplitude in lead V2 ≤ R-wave amplitude in lead V3.Results: PRWP occurred in 213 subjects (3.1%). During the follow-up period of 24.3 ± 10.4 years, 3723 subjects (54.3%) died. PRWP was associated with older age, higher prevalence of heart failure and CAD, and β-blocker medication. In multivariate analyses, PRWP was associated with SCD (hazard ratio [HR] 2.13; 95% confidence interval [CI] 1.34-3.39), cardiac death (HR 1.75; 95% CI 1.35-2.15), and all-cause mortality (HR 1.29; 95% CI 1.08-1.54). In the subgroup with CAD, PRWP had a stronger association with cardiac mortality (HR 1.71; 95% CI 1.19-2.46) than in the subgroup without CAD, while the association with SCD was significant only in the subgroup with CAD (HR 2.62; 95% CI 1.38-4.98).Conclusion: PRWP was associated with adverse prognosis in the general population and with SCD in subjects with CAD. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the impact of glaucoma on health‐related quality of life (HRQoL) and mental health in the ageing population of Finland. Methods: Altogether 7380 and 5774 Finnish individuals aged 30 years and older with known eye disease status were studied in 2000 and 2011, respectively, in two population‐based surveys, including an 11‐year follow‐up of 4683 participants. Data on HRQoL (EQ‐5D‐3L, 15D), depression (BDI), psychological distress (GHQ‐12) and eye disease diagnoses were obtained from self‐reported assessments. Information on glaucoma was complemented with the medication, diagnosis and eye surgery data obtained from the Finnish Health Registries. Distance visual acuity was assessed using the Snellen eye chart test. In logistic regression analyses, data were corrected for age, gender and the most common comorbidities. Results: Glaucoma patients with verified diagnosis (n = 192 in 2000, n = 202 in 2011) and individuals with self‐suspected glaucoma (n = 100 in 2000, n = 41 in 2011) showed a significant decrease in their HRQoL. Glaucoma was also associated with worsened overall mental health based on BDI and GHQ‐12 results. Visual impairment associated with glaucoma is the major determinant of the reduced HRQoL and mental health. Neither glaucoma medication nor glaucoma surgery affected these parameters. The impact of glaucoma on HRQoL and mental health diminished between 2000 and 2011 in a cross‐sectional setting. The newly diagnosed glaucoma during the 11‐year follow‐up had a minimal effect on them. Conclusion: Glaucoma patients show reduced HRQoL and mental health, which is associated with vision loss regardless of the awareness or treatment of the disease. However, this effect seems to be diminishing over time, and the newly diagnosed glaucoma did not show a significant effect on either HRQoL or mental health. [ABSTRACT FROM AUTHOR]

Early repolarization (ER) has been linked to the risk of sudden cardiac death (SCD) in the general population, although controversy remains regarding risks across various subgroups. The purpose of this study was to investigate whether age and sex influence the prognostic significance of ER. We evaluated the 12-lead electrocardiograms of 6631 Finnish general population subjects age ≥30 years (mean age 50.1 ± 13.9 years; 44.5% men) for the presence of ER (J-point elevation ≥0.1 mV in ≥2 inferior/lateral leads) and followed them for 24.4 ± 10.3 years. We analyzed the association between ER and the risk of SCD, cardiac death, and all-cause mortality in subgroups according to age (<50 or ≥50 years) and sex. ER was present in 367 of the 3305 subjects age <50 years and in 426 of 3326 subjects ≥50 years. ER was not associated with any of the endpoints in the entire study population. After adjusting for clinical factors, ER was associated with SCD (hazard ratio [HR] 1.88; 95% confidence interval [CI] 1.16–3.07) in subjects <50 but not in older subjects (interaction between ER and age group, P =.048). In the younger subgroup, women with ER had a high risk of SCD (HR 4.11; 95% CI 1.41–12.03), whereas among men ER was not associated with SCD. Finally, ER was not associated with cardiac mortality or all-cause mortality in either age group. ER is associated with SCD in subjects younger than 50 years, particularly in women, but not in subjects 50 years and older. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) has been associated with coronary mortality. Yet, data about the association between COPD and acute myocardial infarction (MI) remain scarce. We aimed to study airway obstruction as a predictor of MI and coronary mortality among 5576 Finnish adults who participated in a national health examination survey between 1978 and 1980. Subjects underwent spirometry, had all necessary data, showed no indications of cardiovascular disease at baseline, and were followed up through record linkage with national registers through 2011. The primary outcome consisted of a major coronary event—that is, hospitalization for MI or coronary death, whichever occurred first. We specified obstruction using the lower limit of normal categorization. Through multivariate analysis adjusted for potential confounding factors for coronary heart disease, hazard ratios (HRs) (with the 95% confidence intervals in parentheses) of a major coronary event, MI, and coronary death reached 1.06 (0.79–1.42), 0.84 (0.54–1.31), and 1.40 (1.04–1.88), respectively, in those with obstruction compared to others. However, in women aged 30–49 obstruction appeared to predict a major coronary event, where the adjusted HR reached 4.21 (1.73–10.28). In conclusion, obstruction appears to predict a major coronary event in younger women only, whereas obstruction closely associates with the risk of coronary death independent of sex and age. [ABSTRACT FROM AUTHOR]

Background: Meniscal lesions are among the most common injuries of the knee, yet limited epidemiologic data is available on their risk factors. We investigated the association of lifestyle factors and physical strenuousness of work on knee injuries with a focus on meniscal lesions.Methods: We examined a nationally representative sample of persons aged 30 to 59 years, who participated in a comprehensive health examination (the Mini-Finland Health Survey). Subjects without any injury or osteoarthritis in the knee joint at baseline (n = 4713) were subsequently followed via the National Hospital Discharge Register up to 30 years.Results: During the follow-up, 338 knee injuries were identified of which 224 were meniscal lesions. Obesity and regular leisure time physical exercise were associated with an increased risk of first hospitalization due to meniscal lesions (hazard ratio (HR) 1.62 and 95% confidence interval (CI) 1.06-2.48 and 1.53, 95% CI 1.05-2.23, respectively). The types of sports predicting the highest risk of meniscal lesions were ballgames, gymnastics and jogging. Physical strenuousness of work did not predict meniscal lesion. The hazard of other knee injury was increased among those reporting irregular or regular physical exercise at baseline (HR 1.64, 95% CI 1.03-2.64 and 1.88 CI 1.05-2.36, respectively). Smoking or alcohol intake were not associated with knee injuries.Conclusions: Better safety measures in high-risk sports and weight control would likely improve the prevention of meniscal lesions in populations. [ABSTRACT FROM AUTHOR]

There is little long-term follow-up data concerning the association between past pulmonary tuberculosis (TB), airway obstruction and mortality. We aimed to analyse a national health examination survey data from 6701 adult Finns undergoing spirometry between 1978 and 1980 (follow-up through 2013). We identified TB either through a disease history or by a TB-indicative scar on a chest x-ray. We specified obstruction using the lower limit of normal (LLN) and classified severity using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1–4. After adjusting for smoking and other confounders, past TB associated with obstruction. Compared to non-TB patients, the adjusted odds ratio (OR; 95% CI) of obstruction reached 2.21 (1.52–3.21) among patients with a scar recorded by one radiologist, 2.48 (1.63–3.78) when recorded by both radiologists and 4.59 (2.86–7.37) among patients with a disease history. Among those with neither past TB nor obstruction, with past TB only, with an obstruction only and with both, we found hazard ratios (HRs; 95% CIs) for subsequent mortality of 1.00 (reference), 1.11 (1.03–1.20), 1.62 (1.31–2.00) and 1.77 (1.45–2.16), adjusted for age, gender, smoking, body mass index (BMI), physical activity, education and general health. In conclusion, past TB strongly determines obstruction, although on its own quite weakly predicts premature death. TB and obstruction combined predict an additive mortality pattern. [ABSTRACT FROM PUBLISHER]

Background and aim. Clinically diagnosed coeliac disease patients carry an increased risk of mortality. As coeliac disease is markedly underdiagnosed, we aimed to quantify the risk of mortality in subjects with unrecognized and thus untreated coeliac disease. Method. Blood samples from 6,987 Finnish adults were drawn in 1978-80, and sera were tested for immunoglobulin A (IgA)-class tissue transglutaminase antibodies (Eu-tTG) in 2001. Positive sera were further analysed for endomysial (EMA) and tissue transglutaminase antibodies by another test (Celikey tTG). EMA- and Celikey tTG-positive cases were compared to negatives as regards mortality in up to 28 years of surveillance, yielding a total follow-up of 147,646 person years. Dates and causes of death were extracted from the nation-wide database. Results. Altogether 74 (1.1%) of the participants were EMA- and 204 (2.9%) Celikey tTG-positive. The age- and sex-adjusted relative risk of overall mortality was not increased in either EMA (0.78, 95% CI 0.52-1.18) or Celikey tTG (1.19, 95% CI 0.99-1.42) -positive subjects. However, antibody-positive cases evinced a tendency to die from lymphoma, stroke, and diseases of the respiratory system. Conclusions. The prognosis of unrecognized coeliac disease was good as regards overall mortality, which does not support screening of asymptomatic coeliac disease cases. [ABSTRACT FROM AUTHOR]

Objective: We investigated whether combining several ECG abnormalities would identify general population subjects with a high sudden cardiac death (SCD) risk.Methods: In a sample of 6830 participants (mean age 51.2±13.9 years; 45.5% male) in the Mini-Finland Health Survey, a general population cohort representative of the Finnish adults aged ≥30 years conducted in 1978-1980, we examined their ECGs, following subjects for 24.3±10.4 years. We analysed the association between individual ECG abnormalities and 10-year SCD risk and developed a risk score using five ECG abnormalities independently associated with SCD risk: heart rate >80 beats per minute, PR duration >220 ms, QRS duration >110 ms, left ventricular hypertrophy and T-wave inversion. We validated the score using an external general population cohort of 10 617 subjects (mean age 44.0±8.5 years; 52.7% male).Results: No ECG abnormalities were present in 4563 subjects (66.8%), while 96 subjects (1.4%) had ≥3 ECG abnormalities. After adjusting for clinical factors, the SCD risk increased progressively with each additional ECG abnormality. Subjects with ≥3 ECG abnormalities had an HR of 10.23 (95% CI 5.29 to 19.80) for SCD compared with those without abnormalities. The risk score similarly predicted SCD risk in the validation cohort, in which subjects with ≥3 ECG abnormalities had HR 10.82 (95% CI 3.23 to 36.25) for SCD compared with those without abnormalities.Conclusion: The ECG risk score successfully identified general population subjects with a high SCD risk. Combining ECG risk markers may improve the risk stratification for SCD. [ABSTRACT FROM AUTHOR]

Background: Early repolarization (ER) has been linked to the risk of sudden cardiac death (SCD) in the general population, although controversy remains regarding risks across various subgroups.Objective: The purpose of this study was to investigate whether age and sex influence the prognostic significance of ER.Methods: We evaluated the 12-lead electrocardiograms of 6631 Finnish general population subjects age ≥30 years (mean age 50.1 ± 13.9 years; 44.5% men) for the presence of ER (J-point elevation ≥0.1 mV in ≥2 inferior/lateral leads) and followed them for 24.4 ± 10.3 years. We analyzed the association between ER and the risk of SCD, cardiac death, and all-cause mortality in subgroups according to age (<50 or ≥50 years) and sex.Results: ER was present in 367 of the 3305 subjects age <50 years and in 426 of 3326 subjects ≥50 years. ER was not associated with any of the endpoints in the entire study population. After adjusting for clinical factors, ER was associated with SCD (hazard ratio [HR] 1.88; 95% confidence interval [CI] 1.16-3.07) in subjects <50 but not in older subjects (interaction between ER and age group, P = .048). In the younger subgroup, women with ER had a high risk of SCD (HR 4.11; 95% CI 1.41-12.03), whereas among men ER was not associated with SCD. Finally, ER was not associated with cardiac mortality or all-cause mortality in either age group.Conclusion: ER is associated with SCD in subjects younger than 50 years, particularly in women, but not in subjects 50 years and older. [ABSTRACT FROM AUTHOR]

Background--T-wave inversion in right precordial leads V1, to V3 is a relatively common finding in a 12-lead ECG of children and adolescents and is infrequently found also in healthy adults. However, this ECG pattern can also be the first presentation of arrhythmogenic right ventricular cardiomyopathy. The prevalence and prognostic significance of T-wave inversions in the middle-aged general population are not well known. Methods and Results--We evaluated 12-lead ECGs of 10 899 Finnish middle-aged subjects (52% men, mean age 44±8.5 years) recorded between 1966 and 1972 for the presence of inverted T waves and followed the subjects for 30± 11 years. Primary end points were all-cause mortality, cardiac mortality, and arrhythmic death. T-wave inversions in right precordial leads V1, to V3 were present in 54 (0.5%) of the subjects. In addition, 76 (0.7%) of the subjects had inverted T waves present only in leads other than V1, to V3. Right precordial T-wave inversions did not predict increased mortality (not significant for all end points). However, inverted T waves in leads other than V1, to V3 were associated with an increased risk of cardiac and arrhythmic death (P<0.001 for both). Conclusions--T-wave inversions in right precordial leads are relatively rare in the general population, and are not associated with adverse outcome. Increased mortality risk associated with inverted T waves in other leads may reflect the presence of an underlying structural heart disease. INSET: CLINICAL PERSPECTIVE. [ABSTRACT FROM AUTHOR]

Background-Early repolarization (ER) in inferior/lateral leads of standard ECGs increases the risk of arrhythmic death. We tested the hypothesis that variations in the ST-segment characteristics after the ER waveforms may have prognostic importance. Methods and Results-ST segments after ER were classified as horizontal/descending or rapidly ascending/upsioping on the basis of observations from 2 independent samples of young healthy athletes from Finland (n = 62) and the United States (n503), where ascending type was the dominant and common form of ER. Early repolarization was present in 27/62 (44%) of the Finnish athletes and 151/503 (30%) of the US athletes, and all but! of the Finnish (96%) and 91/107 (85%) of US athletes had an ascending/upsloping ST variant after ER. Subsequently, ECGs from a general population of 10 864 middle-aged subjects were analyzed to assess the prognostic modulation of ER-associated risk by ST-segment variations. Subjects with ER≥0.1 mV and horizontal/descending ST variant (n=412) had an increased hazard ratio of arrhythmic death (relative risk 1.43; 95% confidence interval 1.05 to 1.94). When modeled for higher amplitude ER (>0.2 mV) in inferior leads and horizontal/descending ST-segment variant, the hazard ratio of arrhythmic death increased to 3.14 (95% confidence interval 1.56 to 6.30). However, in subjects with ascending ST variant, the relative risk for arrhythmic death was not increased (0.89; 95% confidence interval 0.52 to 1.55). Conclusions-ST-segment morphology variants associated with ER separates subjects with and without an increased risk of arrhythmic death in middle-aged subjects. Rapidly ascending ST segments after the J-point, the dominant ST pattern in healthy athletes, seems to be a benign variant of ER. [ABSTRACT FROM AUTHOR]