Showing papers by "Seppo Koskinen published in 2017"

Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk

Abstract: Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure–raising genetic variants on future cardiovascular disease risk.

Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19.1 million participants

Abstract: Summary Background Raised blood pressure is an important risk factor for cardiovascular diseases and chronic kidney disease. We estimated worldwide trends in mean systolic and mean diastolic blood pressure, and the prevalence of, and number of people with, raised blood pressure, defined as systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher. Methods For this analysis, we pooled national, subnational, or community population-based studies that had measured blood pressure in adults aged 18 years and older. We used a Bayesian hierarchical model to estimate trends from 1975 to 2015 in mean systolic and mean diastolic blood pressure, and the prevalence of raised blood pressure for 200 countries. We calculated the contributions of changes in prevalence versus population growth and ageing to the increase in the number of adults with raised blood pressure. Findings We pooled 1479 studies that had measured the blood pressures of 19·1 million adults. Global age-standardised mean systolic blood pressure in 2015 was 127·0 mm Hg (95% credible interval 125·7–128·3) in men and 122·3 mm Hg (121·0–123·6) in women; age-standardised mean diastolic blood pressure was 78·7 mm Hg (77·9–79·5) for men and 76·7 mm Hg (75·9–77·6) for women. Global age-standardised prevalence of raised blood pressure was 24·1% (21·4–27·1) in men and 20·1% (17·8–22·5) in women in 2015. Mean systolic and mean diastolic blood pressure decreased substantially from 1975 to 2015 in high-income western and Asia Pacific countries, moving these countries from having some of the highest worldwide blood pressure in 1975 to the lowest in 2015. Mean blood pressure also decreased in women in central and eastern Europe, Latin America and the Caribbean, and, more recently, central Asia, Middle East, and north Africa, but the estimated trends in these super-regions had larger uncertainty than in high-income super-regions. By contrast, mean blood pressure might have increased in east and southeast Asia, south Asia, Oceania, and sub-Saharan Africa. In 2015, central and eastern Europe, sub-Saharan Africa, and south Asia had the highest blood pressure levels. Prevalence of raised blood pressure decreased in high-income and some middle-income countries; it remained unchanged elsewhere. The number of adults with raised blood pressure increased from 594 million in 1975 to 1·13 billion in 2015, with the increase largely in low-income and middle-income countries. The global increase in the number of adults with raised blood pressure is a net effect of increase due to population growth and ageing, and decrease due to declining age-specific prevalence. Interpretation During the past four decades, the highest worldwide blood pressure levels have shifted from high-income countries to low-income countries in south Asia and sub-Saharan Africa due to opposite trends, while blood pressure has been persistently high in central and eastern Europe. Funding Wellcome Trust.

CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits

Abstract: There are few examples of robust associations between rare copy number variants (CNVs) and complex continuous human traits Here we present a large-scale CNV association meta-analysis on anthropometric traits in up to 191,161 adult samples from 26 cohorts The study reveals five CNV associations at 1q211, 3q29, 7q1123, 11p142, and 18q2132 and confirms two known loci at 16p112 and 22q1121, implicating at least one anthropometric trait The discovered CNVs are recurrent and rare (001-02%), with large effects on height (>24 cm), weight (>5 kg), and body mass index (BMI) (>35 kg/m2) Burden analysis shows a 041 cm decrease in height, a 0003 increase in waist-to-hip ratio and increase in BMI by 014 kg/m2 for each Mb of total deletion burden (P = 25 × 10-10, 60 × 10-5, and 29 × 10-3) Our study provides evidence that the same genes (eg, MC4R, FIBIN, and FMO5) harbor both common and rare variants affecting body size and that anthropometric traits share genetic loci with developmental and psychiatric disordersIndividual SNPs have small effects on anthropometric traits, yet the impact of CNVs has remained largely unknown Here, Kutalik and co-workers perform a large-scale genome-wide meta-analysis of structural variation and find rare CNVs associated with height, weight and BMI with large effect sizes

A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk

Abstract: To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.

Gender-related differences in the multi-pathway effect of social determinants on quality of life in older age-the COURAGE in Europe project.

Abstract: Purpose Gender-related differences in life expectancy, prevalence of chronic conditions and level of disability in the process of ageing have been broadly described. Less is known about social determinants, which may have different impacts on quality of life in men and women. The investigation aims to reveal gender-related differences in social determinants on quality of life assessed by a multi-pathway model including health, social, demographic and living place characteristics.

Contrast-enhanced ultrasound using sulfur hexafluoride is safe in the pediatric setting.

Abstract: BackgroundContrast-enhanced ultrasound (CEUS) by using sulfur hexafluoride microbubbles is not licensed for use in children, but its off-label use is widespread.PurposeTo outline our experience wit...

Incidence and Imaging Findings of Costal Cartilage Fractures in Patients with Blunt Chest Trauma: A Retrospective Review of 1461 Consecutive Whole-Body CT Examinations for Trauma.

Abstract: Purpose To assess the incidence of costal cartilage (CC) fractures in whole-body computed tomographic (CT) examinations for blunt trauma and to evaluate distribution of CC fractures, concomitant injuries, mechanism of injury, accuracy of reporting, and the effect on 30-day mortality. Materials and Methods Institutional review board approval was obtained for this retrospective study. All whole-body CT examinations for blunt trauma over 36 months were reviewed retrospectively and chest trauma CT studies were evaluated by a second reader. Of 1461 patients who underwent a whole-body CT examination, 39% (574 of 1461) had signs of thoracic injuries (men, 74.0% [425 of 574]; mean age, 46.6 years; women, 26.0% [149 of 574]; mean age, 48.9 years). χ2 and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Interobserver agreement was calculated by using Cohen kappa values. Results A total of 114 patients (men, 86.8% [99 of 114]; mean age, 48.6 years; women, 13.2% [15 of 114]; mean age, 45.1 years) had 221 CC fractures. The incidence was 7.8% (114 of 1461) in all whole-body CT examinations and 19.9% (114 of 574) in patients with thoracic trauma. Cartilage of rib 7 (21.3%, 47 of 221) was most commonly injured. Bilateral multiple consecutive rib fractures occurred in 36% (41 of 114) versus 14% (64 of 460) in other patients with chest trauma (OR, 3.48; 95% CI: 2.18, 5.53; P < .0001). Hepatic injuries were more common in patients with chest trauma with CC fractures (13%, 15 of 114) versus patients with chest trauma without CC fractures (4%, 18 of 460) (OR, 3.72; 95% CI: 1.81, 7.64; P = .0001), as well as aortic injuries (n = 4 vs n = 0; P = .0015; OR, unavailable). Kappa value for interobserver agreement in detecting CC fractures was 0.65 (substantial agreement). CC fractures were documented in 39.5% (45 of 114) of primary reports. The 30-day mortality of patients with CC fractures was 7.02% (eight of 114) versus 4.78% (22 of 460) of other patients with chest trauma (OR, 1.50; 95% CI: 0.65, 3.47; P = .3371). Conclusion CC fractures are common in high-energy blunt chest trauma and often occur with multiple consecutive rib fractures. Aortic and hepatic injuries were more common in patients with CC fractures than in patients without CC fractures. © RSNA, 2017.

Association of experienced and evaluative well-being with health in nine countries with different income levels: a cross-sectional study.

Abstract: It is important to know whether the relationships between experienced and evaluative well-being and health are consistent across countries with different income levels. This would allow to confirm whether the evidence found in high income countries is the same as in low- and middle-income countries and to suggest policy recommendations that are generalisable across countries. We assessed the association of well-being with health status; analysed the differential relationship that positive affect, negative affect, and evaluative well-being have with health status; and examined whether these relationships are similar across countries. In this cross-sectional study, interviews were conducted amongst 53,269 adults from nine countries in Africa, Asia, Europe, and Latin America. Evaluative well-being was measured with a short version of the World Health Organization (WHO) Quality of Life instrument, and experienced well-being was measured with the Day Reconstruction Method. Decrements in health were assessed with the 12-item version of WHO Disability Assessment Schedule 2.0. Block-wise linear regression and structural equation models were employed. Considering the overall sample, evaluative well-being was more strongly associated with health (β = −0.35) than experienced well-being (β = −0.14), and negative affect was more strongly associated with health (β = 0.10) than positive affect (β = −0.02). The relationship between health and well-being was similar across countries. Lower scores in evaluative well-being and a higher age were the factors more strongly related with a worse health. The different patterns observed across countries may be related to differences in the countries’ gross domestic product, social protection system, economic situation, health care provision, lifestyle behaviours, or living conditions. The fact that evaluative well-being is more predictive of health than experienced well-being suggests that our level of satisfaction with our lives might be more important for our health than the actual emotions than we experience in our day-to-day lives and points out the need of interventions that improve the way people evaluate their lives.

Reasons for non-participation and ways to enhance participation in health examination surveys—the Health 2011 Survey

Abstract: High-participation rates to the health examination surveys are needed to obtain representative information about population health. This study aimed to examine reasons for non-participation and factors that could enhance participation using data from the Health 2011 Survey, conducted in 2011-12 in Finland (N = 8135). The most common reason for non-participation was unsuitable timing or location of the health examinations. Older persons also reported that they were too sick to participate. Flexibility on selection of examination times and places and getting feedback on the measurements were most often mentioned as factors which would increase willingness to participate in the future.

High intensity focused ultrasound (HIFU) in tumor therapy.

Abstract: HIFU (high intensity focused ultrasound) is a method in which high-frequency ultrasound is focused on a tissue in order to achieve a thermal effect and the subsequent percutaneously ablation, or tissue modulation. HIFU is non-invasive and results in an immediate tissue destruction effect corresponding to surgery, either percutaneously or through body cavities. HIFU can be utilized in the treatment of both benign and malignant tumors. In neurological diseases, focused HIFU can be used in the treatment of disorders of the basal ganglia.

Radiocarpal Injuries: Cone Beam Computed Tomography Arthrography, Magnetic Resonance Arthrography, and Arthroscopic Correlation Among 21 Patients

Abstract: Background and Aims:Patients with acute or chronic wrist pain often undergo wrist arthroscopy for evaluation of chondral and ligamentous abnormalities. The purpose of this study was to compare findings of wrist arthroscopy with cone beam computed tomography arthrography and magnetic resonance arthrography.Materials and Methods:Altogether, 21 patients with wrist pain underwent cone beam computed tomography arthrography, magnetic resonance arthrography, and wrist arthroscopy. Chondral surfaces of the scaphoid, lunate, and radius facing the scaphoid and lunate were evaluated. The scapholunate ligament, the lunotriquetral ligament, and the triangular fibrocartilage complex were classified as either intact or torn. Sensitivity, specificity, positive and negative predictive values, and accuracy with 95% confidence intervals were assessed.Results:For chondral lesions (n = 10), cone beam computed tomography arthrograms showed slightly higher specificity than magnetic resonance arthrography. The sensitivity of con...

Seasonal affective disorder and alcohol abuse disorder in a population-based study.

Abstract: Seasonal affective disorder (SAD) is a recurrent major depressive disorder with a seasonal pattern, which is characterized by sad mood, low energy, longer sleep duration and carbohydrate craving. Furthermore, seasonal changes in mood and behavior may be closely related to alcohol use disorder (AUD). Nevertheless, there is scarce research on the study of cognitive impairments in SAD and AUD. We aimed to examine the relationship between the prevalence between SAD and AUD patients, and how cognitive functioning might be related to these variables. To do this, a sample of 8135 Finnish subjects was invited to take part in the population-based Health 2011 Survey, of whom 5903 did participate and 4554 were interviewed for mental health status with the Munich version of Composite International Diagnostic Interview. They also completed the modified Seasonal Pattern Assessment Questionnaire, the Mini–Mental State Examination, the category (animals) verbal fluency test, and the Rey Auditory Verbal Learning Test. Our results reveal the existence of a strong link between SAD and AUD in a large sample of Finnish population, as well as association between SAD and short-term memory problems.

International differences in the risk of death from smoking and obesity: The case of the United States and Finland

Abstract: Despite much interest in the health risks associated with behavioral factors, little is known about whether individuals residing in different countries experience a different set of risks. International comparisons of the death risks from major behavioral factors can shed light on whether features of health systems and epidemiological histories modify the health effects of risky behaviors. We used nationally representative samples and mortality linkages spanning the 1971–2014 period from the United States and Finland to examine cross-national differences in the risks of death from cigarette smoking and obesity. We evaluated both current and former smoking and current and prior obesity. In 1990, the approximate midpoint of our study, the death risks from current smoking were about 55% higher in U.S. women compared to Finnish women, but similar for men in the two countries. Death risks from smoking significantly increased over the period for women in both countries and there was no parallel increase in risks among men. Death risks from obesity did not significantly differ in the two countries and no significant trend in the risks were detected in either country. Reasons for the relatively high and increasing risks from smoking among American women warrant further evaluation.

Genetic analysis of over one million people identifies 535 novel loci for blood pressure

Abstract: High blood pressure is the foremost heritable global risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits to date (systolic, diastolic, pulse pressure) in over one million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also reveal shared loci influencing lifestyle exposures. Our findings offer the potential for a precision medicine strategy for future cardiovascular disease prevention.

CT of facial fracture fixation: an experimental study of artefact reducing methods.

Abstract: Objectives:This study aimed to determine the optimal post-operative CT imaging method that enables best visualization of facial bony structures in the vicinity of osteosynthesis materialMethods:Conducted at Toolo Hospital (Helsinki, Finland), this study relied on scanning a phantom with CBCT, 64-slice CT and high-definition multislice CT with dual-energy scan (providing monochromatic images of 70-, 100-, 120- and 140-keV energy levels) and iterative reconstruction (IR) methods Two radiologists assessed the image quality, and the assessments were analyzed In addition, a physicist performed a semi-quantitative analysis of the metal-induced artefactsResults:The three subjects most easily assessed were the loose screw and both the bone structure and the fracture further away from the screw and the plate Soft tissues adjacent to the screw and the plate remained more difficult for assessment Both image interpreters agreed that the artefacts disturbed their assessments under dual energy Metal artefacts di