Prognostic value of P-wave morphology in general population.

AIMS: To evaluate the prognostic significance of novel P-wave morphology descriptors in general population. METHODS AND RESULTS: Novel P-wave morphology variables were analyzed from orthogonal X-, Y-, Z-leads of the digitized electrocardiogram using a custom-made software in 6906 middle-aged subjects of the Mini-Finland Health Survey. A total of 3747 (54.3%) participants died during the follow-up period of 24.3 ± 10.4 years; 379 (5.5%) of the study population succumbed to sudden cardiac death (SCD), 928 (13.4%) to non-SCD (NSCD) and 2440 (35.3%) patients to non-cardiac death (NCD). In univariate comparisons, most of the studied P-wave morphology parameters had a significant association with all modes of death (P from <0.05 to <0.001). After relevant adjustments in the Cox multivariate hazards model, P-wave morphology dispersion (PMD) still tended to predict SCD [hazard ratio (HR): 1.006, 95% confidence interval (CI): 1.000-1.012, P = 0.05) but not NSCD (HR: 0.999, 95% CI: 0.995-1.003, P = 0.68) or NCD (HR: 0.999, 95% CI: 0.997-1.001, P = 0.44). The P-wave maximum amplitude in the lead Z (P-MaxAmp-Z) predicted SCD even after multivariate adjustments (HR: 1.010, 95% CI: 1.005-1.015, P = 0.0002) but also NSCD (HR: 1.005, 95% CI: 1.002-1.009, P = 0.0005) and NCD (HR: 1.002, 95% CI: 1.000-1.005, P = 0.03). CONCLUSION: Abnormalities of P-wave morphology are associated with the risk of all modes of death in general population. After relevant adjustments, PMD was still closely associated with the risk of SCD but not with NSCD or NCD. P-MaxAmp-Z predicted SCD even after adjustments, however, it also retained its association with NSCD and NCD.

Self-rated work ability as a risk factor for disability retirement.

BACKGROUND: Simple and efficient survey measures to predict staying in or leaving work are needed. We examined the association of single-item self-rated work ability (SRWA) with disability retirement in two large population-based samples and compared the association of SRWA to two other scales, work ability score (WAS) and self-rated health (SRH), used earlier in studies. METHODS: The study population comprised 6034 participants aged 35-58 from the population-based Health 2000 and FinHealth 2017 cohort studies, pooled together. SRWA, WAS and SRH were all classified in three categories: poor, limited and good. A 36-month follow-up for disability retirement via linkage to electronic records was included in the analysis. RESULTS: Of the participants, 195 retired during the follow-up. All three measures strongly predicted disability retirement. Hazard ratio (HR) for poor SRWA (vs. good) was 8.48 [95% confidence interval (CI) 5.41-13.28], WAS 7.99 (95% CI 5.62-11.37) and SRH 5.96 (95% CI 4.17-8.51). HR for limited SRWA (vs. good) was 4.35 (95% CI 3.21-5.91), WAS 3.54 (95% CI 2.49-5.04) and SRH 2.27 (95% CI 1.59-3.23). Taking into account gender, age, education and mental health narrowed the gap between poor and limited vs. good work ability as predictors of disability retirement, but the differences remained clear. CONCLUSIONS: Limited or poor self-rated work ability or health are strong predictors of disability retirement. The SRWA measure is a useful survey-measure of work ability in community-based surveys.

Circulating free testosterone and risk of aggressive prostate cancer: Prospective and Mendelian randomisation analyses in international consortia.

Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02-1.28; Phet  = .0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08-1.34; blood-based: 1.03, 1.01-1.05) and early-onset prostate cancer (MR: 1.37, 1.09-1.73; blood-based: 1.08, 0.98-1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood-based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups.

Changes in healthy and unhealthy working life expectancies among older working-age people in Finland, 2000-2017.

BACKGROUND: Raising the statutory retirement age has been a common policy response to population ageing, but health problems may restrict labour force participation in older ages. We examined the development of healthy and unhealthy working life expectancies in Finland from 2000 to 2017 using different measures of health problems. METHODS: Healthy and unhealthy working life expectancies were calculated for the age range 50-65 years using the Sullivan method. The health measures were limiting long-standing illness, self-rated health, mental health problems and self-assessed work ability. RESULTS: Healthy working life expectancy was highest when health was measured by work ability. From 2000 to 2017, working years in full ability between the ages 50-65 increased from 6.2 (95% confidence interval 5.9-6.4) to 8.2 (8.0-8.5). Healthy working life expectancy increased also when measured by the other indicators. Unhealthy working years also increased, except when health problems were measured by limiting long-standing illness. The share of years in work increased both within the healthy and the unhealthy years, the increase being larger or equally large for the latter. Within the healthy and unhealthy years measured by the other three indicators, the share of working years increased irrespective of whether work ability was full or limited, but the increase was larger for limited work ability. CONCLUSIONS: In Finland, healthy working life expectancy has increased irrespective of how health is measured but also working with health problems has become more prevalent. The estimates for healthy working years are highest when a direct measure of work ability is used.

Incidence trends and risk factors of lung cancer in never smokers: Pooled analyses of seven cohorts.

The trends in incidence of lung cancer in never smokers are unclear as well as the significance of risk factors. We studied time trends in the incidence and risk factors of lung cancer in never smokers in Finland in a large, pooled cohort. We pooled data from seven Finnish health cohorts from the period between 1972 and 2015 with 106 193 never smokers. The harmonised risk factors included education, alcohol consumption, physical activity, height and BMI. We retrieved incident lung cancers from the nation-wide Finnish Cancer Registry. We estimated average annual percent change (AAPC) and the effects of risk factors on cause-specific hazard ratios (HRs) of lung cancer using Poisson regression. We detected 47 lung cancers in never smoking men (n = 31 859) and 155 in never smoking women (n = 74 334). The AAPC of lung cancer incidence was -3.30% (95% confidence interval [CI]: -5.68% to -0.88%, P = .009) in never smoking men and 0.00% (95% CI: -1.57% to 1.60%, P = .996) in never smoking women. Of the five studied risk factors only greater height in women had a statistically significant increased risk of lung cancer (multivariate HR = 1.84, 95%CI: 1.08 to 3.12). It is plausible that tobacco control measures focused on working places have reduced passive smoking among men more than among women, which could explain the declining trend in lung cancer incidence in never smoker men but not in never smoker women. As tobacco control measures have not been targeted to domestic environments, it is likely that women's exposure to passive smoking has continued longer.

Prevalence and 11-year incidence of common eye diseases and their relation to health-related quality of life, mental health, and visual impairment.

PURPOSE: To study the prevalence and incidence of the most common eye diseases and their relation to health-related quality of life (HRQoL), depression, psychological distress, and visual impairment in the aging population of Finland. METHODS: Our study was based on two nationwide health surveys conducted in 2000 and 2011. Eye disease status data were obtained from 7379 and 5710 individuals aged 30 + years, of whom 4620 partook in both time points. Both surveys included identical indicators of HRQoL (EuroQol-5 Dimension [EQ-5D], 15D), depression (Beck Depression Inventory [BDI]), psychological distress (General Health Questionnaire-12 [GHQ-12]), visual acuity, and self-reported eye diseases. We assessed the impact of known eye diseases on these factors, adjusted for age, gender, and co-morbidities. RESULTS: Prevalence of self-reported eye diseases was 3.1/2.7% for glaucoma, 8.1/11.4% for cataract, and 3.4/3.8% for retinal degeneration in 2000 and 2011, and the average incidence between 2000 and 2011 was 22, 109, and 35 /year/10,000 individuals, respectively. These eye diseases were associated with a significant decrease in EQ-5D and 15D index scores in both time points. BDI and GHQ-12 scores were also worsened, with some variation between different eye diseases. Impaired vision was, however, the strongest determinant of declined HRQoL. During the 11-year follow-up the effect of eye diseases on HRQoL and mental health diminished. CONCLUSION: Declined HRQoL associated with eye diseases is more related to impaired vision than the awareness of the disease itself, and this declining effect diminished during the follow-up. Therefore, information directed to the public on the risks and prevention of blindness can and should be strengthened to prevent the deleterious effects of visual impairment.

The prognostic significance of T-wave inversion according to ECG lead group during long-term follow-up in the general population.

BACKGROUND: Inverted T waves in the electrocardiogram (ECG) have been associated with coronary heart disease (CHD) and mortality. The pathophysiology and prognostic significance of T-wave inversion may differ between different anatomical lead groups, but scientific data related to this issue is scarce. METHODS: A representative sample of Finnish subjects (n = 6,354) aged over 30 years underwent a health examination including a 12-lead ECG in the Health 2000 survey. ECGs with T-wave inversions were divided into three anatomical lead groups (anterior, lateral, and inferior) and were compared to ECGs with no pathological T-wave inversions in multivariable-adjusted Fine-Gray and Cox regression hazard models using CHD and mortality as endpoints. RESULTS: The follow-up for both CHD and mortality lasted approximately fifteen years (median value with interquartile ranges between 14.9 and 15.3). In multivariate-adjusted models, anterior and lateral (but not inferior) T-wave inversions associated with increased risk of CHD (HR: 2.37 [95% confidence interval 1.20-4.68] and 1.65 [1.27-2.15], respectively). In multivariable analyses, only lateral T-wave inversions associated with increased risk of mortality in the entire study population (HR 1.51 [1.26-1.81]) as well as among individuals with no CHD at baseline (HR 1.59 [1.29-1.96]). CONCLUSIONS: The prognostic information of inverted T waves differs between anatomical lead groups. T-wave inversion in the anterior and lateral lead groups is independently associated with the risk of CHD, and lateral T-wave inversion is also associated with increased risk of mortality. Inverted T wave in the inferior lead group proved to be a benign phenomenon.

Long-term outcome of intraventricular conduction delays in the general population.

BACKGROUND: Previous population studies have presented conflicting results regarding the prognostic impact of intraventricular conduction delays (IVCD). METHODS: We studied long-term prognostic impact and the association with comorbidities of eight IVCDs in a random sample of 6,299 Finnish subjects (2,857 men and 3,442 women, mean age 52.8, SD 14.9 years) aged 30 or over who participated in the health examination including 12-lead ECG. For left bundle branch block (LBBB) and non-specific IVCD (NSIVCD), two different definitions were used. RESULTS: During 16.5 years' follow-up, 1,309 of the 6,299 subjects (20.8%) died and of these 655 (10.4%) were cardiovascular (CV) deaths. After controlling for known clinical risk factors, the hazard ratio for CV death, compared with individuals without IVCD, was 1.55 for the Minnesota definition of LBBB (95% confidence interval 1.04-2.31, p = .032) and 1.27 (95% confidence interval 0.80-2.02, p = .308) for the Strauss' definition of LBBB. Subjects with NSIVCD were associated with twofold to threefold increase in CV mortality depending on the definition. While right bundle branch block, left anterior fascicular block and incomplete bundle branch blocks were associated with seemingly higher mortality, this was no longer the case after adjustment for age and sex. The presence of R-R' pattern was not associated with any adverse outcome. CONCLUSIONS: In a population study with long-term follow-up, NSIVCD and Minnesota definition of LBBB were independently associated with CV mortality. Other IVCDs had no significant impact on prognosis. The prognostic impact of LBBB and NSIVCD was affected by the definition of the conduction disorder.

Prognostic significance of flat T-waves in the lateral leads in general population.

BACKGROUND: Negative T-waves are associated with sudden cardiac death (SCD) risk in the general population. Whether flat T-waves also predict SCD is not known. The aim of the study was to examine the clinical characteristics and risk of SCD in general population subjects with flat T-waves. METHODS: We examined the electrocardiograms of 6750 Finnish general population adults aged ≥30 years and classified the subjects into 3 groups: 1) negative T-waves with an amplitude ≥0.1 mV in ≥2 of the leads I, II, aVL, V4-V6, 2) negative or positive low amplitude T-waves with an amplitude <0.1 mV and the ratio of T-wave and R-wave <10% in ≥2 of the leads I, II, aVL, V4-V6, and 3) normal positive T-waves (not meeting the aforesaid criteria). The association between T-wave classification and SCD was assessed during a 10-year follow-up. RESULTS: A total of 215 (3.2%) subjects had negative T-waves, 856 (12.7%) flat T-waves, and 5679 (84.1%) normal T-waves. Flat T-wave subjects were older and had more often cardiovascular morbidities compared to normal T-wave subjects, while negative T-wave subjects were the oldest and had most often cardiovascular morbidities. After adjusting for multiple factors, both flat T-waves (hazard ratio [HR] 1.81; 95% confidence interval [CI] 1.13-2.91) and negative T-waves (HR 3.27; 95% CI 1.85-5.78) associated with SCD. CONCLUSIONS: Cardiovascular risk factors and disease are common among subjects with flat T-waves, but these minor T-wave abnormalities are also independently associated with increased SCD risk.

Orthogonal P-wave morphology, conventional P-wave indices, and the risk of atrial fibrillation in the general population using data from the Finnish Hospital Discharge Register.

AIMS: Identifying subjects at high and low risk of atrial fibrillation (AF) is of interest. This study aims to assess the risk of AF associated with electrocardiographic (ECG) markers linked to atrial fibrosis: P-wave prolongation, 3rd-degree interatrial block, P-terminal force in lead V1, and orthogonal P-wave morphology. METHODS AND RESULTS: P-wave parameters were assessed in a representative Finnish population sample aged ≥30 years (n = 7217, 46.0% male, mean age 51.4 years). Subjects (n = 5489) with a readable ECG including the orthogonal leads, sinus rhythm, and a predefined orthogonal P-wave morphology type [positive in leads X and Y and either negative (Type 1) or ± biphasic (Type 2) in lead Z; Type 3 defined as positive in lead X and ± biphasic in lead Y], were followed 10 years from the baseline examinations (performed 1978-80). Subjects discharged with AF diagnosis after any-cause hospitalization (n = 124) were defined as having developed AF. Third-degree interatrial block was defined as P-wave ≥120 ms and the presence of ≥2 ± biphasic P waves in the inferior leads. Hazard ratios (HRs) and confidence intervals (CIs) were assessed with Cox models. Third-degree interatrial block (n = 103, HR 3.18, 95% CI 1.66-6.13; P = 0.001) and Type 3 morphology (n = 216, HR 3.01, 95% CI 1.66-5.45; P < 0.001) were independently associated with the risk of hospitalization with AF. Subjects with P-wave <110 ms and Type 1 morphology (n = 2074) were at low risk (HR 0.46, 95% CI 0.26-0.83; P = 0.006), compared to the rest of the subjects. CONCLUSION: P-wave parameters associate with the risk of hospitalization with AF.

Long-term prognostic significance of the ST level and ST slope in the 12­lead ECG in the general population.

BACKGROUND: Even minor ST depression in the electrocardiogram (ECG) is associated with cardiovascular disease and increased mortality. There is limited data on the prognostic significance of ST-level changes in the general population. SUBJECTS AND METHODS: A random sample of Finnish subjects (n = 6354) aged over 30 years (56.1% women) underwent a health examination including a 12­lead ECG in the Health 2000 survey. The effects of relative ST level as a continuous variable and ST slope (upsloping, horizontal, downsloping) in three different lead groups were analyzed using a multi-adjusted Cox proportional hazard model separately for men and women with total mortality as endpoint. RESULTS: The follow-up lasted for 13.7 (SD 3.3) years for men and 13.9 (SD 3.1) years for women. Lower lateral ST levels were associated with all-cause mortality in multi-adjusted models in both genders (at J + 80 ms hazard ratio [HR] 0.64 for a change of 1.0 mm [95% confidence interval 0.49-0.84, p = 0.002] for men and HR 0.61 [0.48-0.78, p < 0.001] for women). Associated coronary heart disease had no major influence on the results. Exclusion of subjects with ECG signs of left ventricular hypertrophy from the analyses increased the mortality risk of lower lateral ST levels in men but decreased it in women. For the anterior and inferior lead groups, no statistically significant difference was seen after multivariate adjustment. ST slope was not an independent predictor of mortality after multivariate adjustment. CONCLUSION: Lower ST level in the lateral ECG leads is an independent prognostic factor to predict all-cause mortality in the general population.

Gender differences in prevalence and prognostic value of fragmented QRS complex.

BACKGROUND: Fragmented QRS (fQRS) on 12-lead electrocardiogram (ECG) is associated with scarred myocardium and adverse outcome. However, the data on gender differences in terms of its prevalence and prognostic value is sparse. The aim of this study was to evaluate whether gender differences in fQRS exist among subjects drawn from populations with different risk profiles. METHODS: We analyzed fQRS from 12-lead ECG in 953 autopsy-confirmed victims of sudden cardiac death (SCD) (78% men; 67.0 ± 11.4 yrs), 1900 coronary artery disease (CAD) patients with angiographically confirmed stenosis of ≥50% (70% men; 66.6 ± 9.0 yrs, 43% with previous myocardial infarction [MI]), and in 10,904 adults drawn from the Finnish adult general population (52% men; 44.0 ± 8.5 yrs). RESULTS: Prevalence of fQRS was associated with older age, male sex and the history and severity of prior cardiac disease of subjects. Among the general population fQRS was more commonly found among men in comparison to women (20.5% vs. 14.8%, p < 0.001). The prevalence of fQRS rose gradually along with the severity of prior cardiac disease in both genders, yet remained significantly higher in the male population: subjects with suspected or known cardiac disease (25.4% vs. 15.8% p < 0.001), CAD patients without prior MI (39.9% vs. 26.4%, p < 0.001), CAD patients with prior MI (42.9% vs. 31.2%, p < 0.001), and victims of SCD (56.4% vs. 44.4%, p < 0.001). CONCLUSIONS: The prevalence of QRS fragmentation varies in different populations. The fragmentation is clearly related to the underlying cardiac disease in both genders, however women seem to have significantly lower prevalence of fQRS in each patient population in comparison to men.

Low vision status and declining vision decrease Health-Related Quality of Life: Results from a nationwide 11-year follow-up study.

PURPOSE: The impact of visual acuity (VA) on Health-Related Quality of Life (HRQoL) and the cross-sectional and longitudinal differences in HRQoL during the 11-year follow-up were investigated. The aim was to examine the impact declining vision has on HRQoL and to provide comparable data to facilitate the allocation of health-care resources. METHODS: We utilized nationwide health examination surveys carried out by the National Institute for Health and Welfare in 2000 and 2011, providing a representative sampling of the Finnish adult population aged 30 and older. VA was assessed through Snellen E test, and HRQoL scores were evaluated using EQ-5D and 15D questionnaires. Multiple imputations with Markov chain Monte Carlo method was used to utilize the data more effectively. Regression analyses were conducted to assess the impact of declining VA on HRQoL, adjusted for incident comorbidities. RESULTS: Lower VA status was associated with significantly lower HRQoL at both time points, most clearly observable below the VA level of 0.5. Declining VA resulted in statistically significant decline in HRQoL during the follow-up, greater with distance than near VA. 15D impairment associated with decline in the distance VA was also clinically meaningful and greater than that associated with any of the examined comorbidities. CONCLUSIONS: HRQoL was significantly and meaningfully impaired even before the threshold of severe vision loss or blindness was reached. The results encourage the improvement of available treatment options aiming to postpone the onset of visual impairment or declining VA, to maintain better quality of life among the population.

Long-term prognostic impact of hyperuricemia in community.

The debate whether an elevated level of serum uric acid (SUA) is an independent marker of cardiovascular risk is still going on. We examined morbidity and mortality related to SUA and hyperuricemia in a well-characterized population with very long follow-up. Study included 4696 participants (aged 30-59 years at baseline) of the coronary heart disease (CHD) Study of the Finnish Mobile Clinic Health Examination Survey. Adjusted hazard ratios (HRs) of hyperuricemia (defined as ≥360 µmol/l and ≥420 µmol/l) and SUA quintiles for mortality and adverse cardiovascular outcomes are reported. During the mean follow up of 30.6 years there were 2723 deaths, 887 deaths for CHD of which 340 were classified as sudden cardiac deaths, 1642 hospitalizations due to CHD and 798 hospitalizations due to congestive heart failure. After adjusting to baseline risk factors and presence of cardiovascular diseases as well as the use of diuretics there were no significant differences in the risk of any of the outcomes when analyzed either according to quintiles of SUA or using a cut-off point SUA ≥360 µmol/l for hyperuricemia. Only a rare finding of hyperuricemia SUA ≥420 µmol/l among women (n = 17, 0.9%) was independently associated with significantly higher risk of mortality (adjusted HR: 2.59, 95% CI: 1.54-4.34) and a combination end-point of major adverse cardiac events (MACEs) (HR: 2.69; 95% CI: 1.56-4.66). SUA was not an independent indicator of morbidity and mortality, with the exception of particularly high levels of SUA among women.

Variation at 2q35 (PNKD and TMBIM1) influences colorectal cancer risk and identifies a pleiotropic effect with inflammatory bowel disease.

To identify new risk loci for colorectal cancer (CRC), we conducted a meta-analysis of seven genome-wide association studies (GWAS) with independent replication, totalling 13 656 CRC cases and 21 667 controls of European ancestry. The combined analysis identified a new risk association for CRC at 2q35 marked by rs992157 (P = 3.15 × 10-8, odds ratio = 1.10, 95% confidence interval = 1.06-1.13), which is intronic to PNKD (paroxysmal non-kinesigenic dyskinesia) and TMBIM1 (transmembrane BAX inhibitor motif containing 1). Intriguingly this susceptibility single-nucleotide polymorphism (SNP) is in strong linkage disequilibrium (r2 = 0.90, D' = 0.96) with the previously discovered GWAS SNP rs2382817 for inflammatory bowel disease (IBD). Following on from this observation we examined for pleiotropy, or shared genetic susceptibility, between CRC and the 200 established IBD risk loci, identifying an additional 11 significant associations (false discovery rate [FDR]) < 0.05). Our findings provide further insight into the biological basis of inherited genetic susceptibility to CRC, and identify risk factors that may influence the development of both CRC and IBD.

Airway obstruction and the risk of myocardial infarction and death from coronary heart disease: a national health examination survey with a 33-year follow-up period.

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.

Participation rates by educational levels have diverged during 25 years in Finnish health examination surveys.

Background: Declining participation rates in health examination surveys may impair the representativeness of surveys and introduce bias into the comparison of results between population groups if participation rates differ between them. Changes in the characteristics of non-participants over time may also limit comparability with earlier surveys. Methods: We studied the association of socio-economic position with participation, and its changes over the past 25 years. Occupational class and educational level are used as indicators of socio-economic position. Data from six cross-sectional FINRISK surveys conducted between 1987 and 2012 in Finland were linked to national administrative registers, which allowed investigation of the differences between survey participants and non-participants. Results: Our results show that individuals with low occupational class or low level of education were less likely to participate than individuals with high occupational class or high level of education. Participation rates decreased in all subgroups of the population but the decline was fastest among those with low level of education. Conclusions: The differences in participation rates must be taken into account to avoid biased estimates because socio-economic position has also been shown to be strongly related to health, health behaviour and biological risk factors. Particular attention should be paid to the recruitment of the less-educated population groups.

Experiences in digitizing and digitally measuring a paper-based ECG archive.

BACKGROUND: No established method for digitizing and digital measuring of paper electrocardiograms (ECG) exists. We describe a paper ECG digitizing and digital measuring process, and report comparability to manual measurements. METHODS: A paper ECG was recorded from 7203 health survey participants in 1978-1980. With specific software, the ECGs were digitized (ECG Trace Tool), and measured digitally (EASE). A sub-sample of 100 ECGs was selected for manual measurements. RESULTS: The measurement methods showed good agreement. The mean global (EASE)-(manual) differences were 1.4ms (95% CI 0.5-2.2) for PR interval, -1.0ms (95% CI -1.5-[-0.5]) for QRS duration, and 11.6ms (95% CI 10.5-12.7) for QT interval. The mean inter-method amplitude differences of RampV5, RampV6, SampV1, TampII and TampV5 ranged from -0.03mV to 0.01mV. CONCLUSIONS: The presented paper-to-digital conversion and digital measurement process is an accurate and reliable method, enabling efficient storing and analysis of paper ECGs.

Mendelian randomisation implicates hyperlipidaemia as a risk factor for colorectal cancer.

While elevated blood cholesterol has been associated with an increased risk of colorectal cancer (CRC) in observational studies, causality is uncertain. Here we apply a Mendelian randomisation (MR) analysis to examine the potential causal relationship between lipid traits and CRC risk. We used single nucleotide polymorphisms (SNPs) associated with blood levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) as instrumental variables (IV). We calculated MR estimates for each risk factor with CRC using SNP-CRC associations from 9,254 cases and 18,386 controls. Genetically predicted higher TC was associated with an elevated risk of CRC (odds ratios (OR) per unit SD increase = 1.46, 95% confidence interval [CI]: 1.20-1.79, p = 1.68 × 10-4 ). The pooled ORs for LDL, HDL, and TG were 1.05 (95% CI: 0.92-1.18, p = 0.49), 0.94 (95% CI: 0.84-1.05, p = 0.27), and 0.98 (95% CI: 0.85-1.12, p = 0.75) respectively. A genetic risk score for 3-hydoxy-3-methylglutaryl-coenzyme A reductase (HMGCR) to mimic the effects of statin therapy was associated with a reduced CRC risk (OR = 0.69, 95% CI: 0.49-0.99, p = 0.046). This study supports a causal relationship between higher levels of TC with CRC risk, and a further rationale for implementing public health strategies to reduce the prevalence of hyperlipidaemia.

Gene × dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry.

Obesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphisms were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjusted WHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjusted WHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.