Human essential hypertension : no significant association of polygenic risk scores with antihypertensive drug responses

Polygenic risk scores (PRSs) for essential hypertension, calculated from>900 genomic loci, were recently found to explain a significant fraction of hypertension heritability and complications. To investigate whether variation of hypertension PRS also captures variation of antihypertensive drug responsiveness, we calculated two different PRSs for both systolic and diastolic blood pressure: one based on the top 793 independent hypertension-associated single nucleotide polymorphisms and another based on over 1 million genome-wide variants. Using our pharmacogenomic GENRES study comprising four different antihypertensive monotherapies (n similar to 200 for all drugs), we identified a weak, but (after Bonferroni correction) statistically nonsignificant association of higher genome-wide PRSs with weaker response to a diuretic. In addition, we noticed a correlation between high genome-wide PRS and electrocardiographic left ventricular hypertrophy. Finally, using data of the Finnish arm of the LIFE study (n=346), we found that PRSs for systolic blood pressure were slightly higher in patients with drug-resistant hypertension than in those with drug-controlled hypertension (p=0.03, not significant after Bonferroni correction). In conclusion, our results indicate that patients with elevated hypertension PRSs may be predisposed to difficult-to-control hypertension and complications thereof. No general association between a high PRS and less efficient drug responsiveness was noticed.Peer reviewe

Waveform prototype-based feature learning for automatic detection of the early repolarization pattern in ECG signals

Objective: Our aim was to develop an automated detection method, for prescreening purposes, of early repolarization (ER) pattern with slur/notch configuration in electrocardiogram (ECG) signals using a waveform prototype-based feature vector for supervised classification. Approach: The feature vectors consist of fragments of the ECG signal where the ER pattern is located, instead of abstract descriptive variables of ECG waveforms. The tested classifiers included linear discriminant analysis, k-nearest neighbor algorithm, and support vector machine (SVM). Main results: SVM showed the best performance in Friedman tests in our test data including 5676 subjects representing 45408 leads. Accuracies of the different classifiers showed results well over 90%, indicating that the waveform prototype-based feature vector is an effective representation of the differences between ECG signals with and without the ER pattern. The accuracy of inferior ER was 92.74% and 92.21% for lateral ER. The sensitivity achieved was 91.80% and specificity was 92.73%. Significance: The algorithm presented here showed good performance results, indicating that it could be used as a prescreening tool of ER, and it provides an additional identification of critical cases based on the distances to the classifier decision boundary, which are close to the 0.1 mV threshold and are difficult to label.Peer reviewe

Waveform prototype-based feature learning for automatic detection of the early repolarization pattern in ECG signals

Objective: Our aim was to develop an automated detection method, for prescreening purposes, of early repolarization (ER) pattern with slur/notch configuration in electrocardiogram (ECG) signals using a waveform prototype-based feature vector for supervised classification. Approach: The feature vectors consist of fragments of the ECG signal where the ER pattern is located, instead of abstract descriptive variables of ECG waveforms. The tested classifiers included linear discriminant analysis, k-nearest neighbor algorithm, and support vector machine (SVM). Main results: SVM showed the best performance in Friedman tests in our test data including 5676 subjects representing 45408 leads. Accuracies of the different classifiers showed results well over 90%, indicating that the waveform prototype-based feature vector is an effective representation of the differences between ECG signals with and without the ER pattern. The accuracy of inferior ER was 92.74% and 92.21% for lateral ER. The sensitivity achieved was 91.80% and specificity was 92.73%. Significance: The algorithm presented here showed good performance results, indicating that it could be used as a prescreening tool of ER, and it provides an additional identification of critical cases based on the distances to the classifier decision boundary, which are close to the 0.1 mV threshold and are difficult to label.Peer reviewe

Genome-wide association study of nocturnal blood pressure dipping in hypertensive patients

Abstract Background Reduced nocturnal fall (non-dipping) of blood pressure (BP) is a predictor of cardiovascular target organ damage. No genome-wide association studies (GWAS) on BP dipping have been previously reported. Methods To study genetic variation affecting BP dipping, we conducted a GWAS in Genetics of Drug Responsiveness in Essential Hypertension (GENRES) cohort (n = 204) using the mean night-to-day BP ratio from up to four ambulatory BP recordings conducted on placebo. Associations with P < 1 × 10− 5 were further tested in two independent cohorts: Haemodynamics in Primary and Secondary Hypertension (DYNAMIC) (n = 183) and Dietary, Lifestyle and Genetic determinants of Obesity and Metabolic Syndrome (DILGOM) (n = 180). We also tested the genome-wide significant single nucleotide polymorphism (SNP) for association with left ventricular hypertrophy in GENRES. Results In GENRES GWAS, rs4905794 near BCL11B achieved genome-wide significance (β = − 4.8%, P = 9.6 × 10− 9 for systolic and β = − 4.3%, P = 2.2 × 10− 6 for diastolic night-to-day BP ratio). Seven additional SNPs in five loci had P values < 1 × 10− 5. The association of rs4905794 did not significantly replicate, even though in DYNAMIC the effect was in the same direction (β = − 0.8%, P = 0.4 for systolic and β = − 1.6%, P = 0.13 for diastolic night-to-day BP ratio). In GENRES, the associations remained significant even during administration of four different antihypertensive drugs. In separate analysis in GENRES, rs4905794 was associated with echocardiographic left ventricular mass (β = − 7.6 g/m2, P = 0.02). Conclusions rs4905794 near BCL11B showed evidence for association with nocturnal BP dipping. It also associated with left ventricular mass in GENRES. Combined with earlier data, our results provide support to the idea that BCL11B could play a role in cardiovascular pathophysiology

Prediction of sudden cardiac death with automated high-throughput analysis of heterogeneity in standard resting 12-lead electrocardiograms

BACKGROUND Heterogeneity of depolarization and repolarization underlies the development of lethal arrhythmias. OBJECTIVE We investigated whether quantification of spatial depolarization and repolarization heterogeneity identifies individuals at risk for sudden cardiac death (SCD). METHODS Spatial R-, J-, and T-wave heterogeneity (RWH, JWH, and TWH, respectively) was analyzed using automated second central moment analysis of standard digital 12-lead electrocardiograms in 5618 adults (2588, 46% men; mean +/- SEM age 50.9 +/- 0.2 years), who took part in the epidemiological Health 2000 Survey as representative of the entire Finnish adult population. RESULTS During the follow-up period of 7.7 +/- 0.2 years, a total of 72 SCDs occurred (1.3%), with an average yearly incidence rate of 0.17% per year. Increased RWH, JWH, and TWH in left precordial leads (V-4-V-6) were univariately associated with SCD (P = 102 mu V) was associated with a 1.7-fold adjusted relative risk for SCD (95% confidence interval [CI] 1.0-2.9; P = .048) and increased JWH (>= 123 mu V) with a 2.0-fold adjusted relative risk for SCD (95% CI 1.2-3.3; P = .006). When both TWH and JWH were above the threshold, the adjusted relative risk for SCD was 2.9-fold (95% CI 1.5-5.7; P = .002). When RWH (>= 470 mu V), JWH, and TWH were all above the threshold, the adjusted relative risk for SCD was 3.2-fold (95% CI 1.4-7.1; P = .009). CONCLUSION Second central moment analysis of standard resting 12-lead electrocardiographic morphology provides an ultrarapid means for the automated measurement of spatial RWH, JWH, and TWH, enabling analysis of high subject volumes and screening for SCD risk in the general population.Peer reviewe

Serial assessment of the electrocardiographic strain pattern for prediction of new‐onset heart failure during antihypertensive treatment: the LIFE study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106144/1/ejhfhfq224.pd

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

JOKAPÄIVÄINEN LEIPÄJONOMME : Sosiaalinen pääoma ja osallisuus leipäjonoasiakkaiden kokemuksissa

Opinnäytetyömme tutkimustehtävä oli selvittää leipäjonojen asiakkaiden kokemuksia osallisuudesta ja sosiaalisesta pääomasta ruoka-avun toimintaympäristössä. Tavoitteenamme oli saada leipäjonon asiakkaiden oma ääni kuuluviin. Tämän kautta halusimme lisätä ymmärrystä kyseisen ympäristön sosiaalisista vaikutuksista ja mahdollisuuksista. Opinnäytetyömme on laadullinen tutkimus, jossa aineisto kerättiin teemahaastattelulla. Haastatteluja toteutettiin kuusi. Haastatteluaineiston myötä pääkäsitteiden sosiaalisen pääoman ja osallisuuden alakäsitteiksi muodostuivat sosiaaliset verkostot, luottamus ja vastavuoroisuus sekä toimijuus, jäsenyys ja huono-osaisuus. Aineisto käsiteltiin teemoittelemalla ja on tarkasteltu suhteessa valittuun teoriaan. Opinnäytetyön tutkimustuloksena toteamme, että aineistomme mukaan tutkimamme leipäjonoympäristöt mahdollistavat yhdistävän sosiaalisen pääoman muodostumisen. Osallisuutta ilmeni sekä vastaanottaja- että kantaaottajatasoilla. Huono-osaisuus esiintyi asiakkaiden kokemuksissa pääosin taloudellisena tekijänä. Jatkotutkimusideoina prosessin aikana esiin nousivat asiakkaiden leipäjonoympäristön ulkopuoliset ihmissuhteet ja sosiaaliset piirit. Näiden lisäksi myös huono-osaisuus omana kokonaisuutenaan sekä sosiaalisen pääoman ja osallisuuden mahdolliset negatiiviset vaikutukset ovat kiinnostavia jatkotutkimuksen kohteita.The purpose of our thesis was to discover whether there can be found elements of involvement and social capital amongst the clients of food distribution. We intended to reach that goal by interviewing six clients. Our thesis is a qualitative research. The method we used to gather our data was the theme interview. Our main themes were social capital and involvement. Our subthemes were formed according to our interviews. The subthemes were social networks, trust and reciprocity, agents, participation and social exclusion. Our main result was that this environment includes possibilities to form social capital and involvement. Factors that affect _ those processes are motivation and activity of individuals and trust and reciprocity to the food queues. A possibility to make a difference had a positive influence on both main themes. Ideas for further research were to investigate the influence of the clients’ social relationships and networks that occur outside the food queues to establish how social exclusion appears on a larger scale, and also whether social capital and involvement include any negative consequences

Ravintola-alan arvonlisäveron alentamisen vaikutus hintoihin ja kuluttajakäyttäytymiseen

Opinnäytetyön tarkoituksena oli selvittää 1.7.2010 tapahtuneen ravintola-alan arvonlisäveron alennuksen vaikutuksia ravintola-alan yritysten tuotteiden hintoihin ja kuluttajakäyttäytymiseen Jyväskylässä. Tavoitteena oli kartoittaa, kuinka alv:n alennus toteutui käytännössä ja miten se vaikutti kuluttajien ostokäyttäytymiseen. Tutkimuksen otantana oli 38 erilaista ravintola-alan yritystä, joiden tuotteiden hintakehitystä seurattiin Jyväskylän alueella. Tutkimuksessa kerättiin yritysten tuotteiden hintatiedot touko-kesäkuussa sekä arvonlisäveron alennuksen jälkeen heinä-elokuussa. Aineistonkeruumenetelmänä käytettiin mystery shopping -menetelmää sekä hyödyntämällä yritysten internetsivuja hintojen seurannassa. Kyselytutkimus toteutettiin sähköisesti Jyväskylän ammattikorkeakoulun opiskelijoille 1.12 - 10.12.2010 välisenä aikana. Tutkimuksen tuloksena selvisi, että ravintola-alan arvonlisäveron alennus jäi toteutumatta täysimääräisenä tuotteiden hinnoissa. Ravintolat reagoivat arvonlisäveron alennukseen eri tavoin. Tutkimukseen valitut ravintolat pystyttiin jakamaan erilaisiin ryhmiin. Jako perustui arvonlisäveron alennuksen vaikutuksiin tuotteiden hintoihin. Sähköisesti toteutetun kyselytutkimuksen otos oli 204 vastaajaa 1 469 vastaajasta, jolloin kyselyn vastausprosentti oli 14. Tutkimus osoitti, että arvonlisäveron alennus ei vaikuttanut kuluttajien ostokäyttäytymiseen. Kuluttajan näkökulmasta arvonlisäveron alennus ei toteutunut toivotulla tavalla. Tutkimusta voidaan hyödyntää tulevaisuudessa pohjana uusille arvonlisäveroa käsitteleville tutkimuksille. Opinnäytetyö oli ajankohtainen, sillä arvonlisäveron alennuksen oletettiin elvyttävän alaa ja lisäävän kulutusta.The aim of the thesis was to find out how the VAT reduction influenced on the restaurant sector. The VAT reduction was effectuated on the first of July 2010. Another aim of the thesis was to study how did restaurants reacted to the VAT reduction in their pricing and how it affected consumer behavior in the Jyväskylä area. In addition, it was to studied how the VAT reduction was carried out and how it affected consumers. The sampling of the research was 38 different restaurants in the Jyväskylä area. The pricing of restaurant products before and after the VAT reduction was observed. The of product prices were gathered from the restaurants’ Internet pages and also by the mystery shopping method. The survey was completed online by sending e-mails to students of JAMK University of Applied Sciences between December 1st 2010 and December 10, 2010. The results of the study showed that the VAT reduction was not realized in the product prices. In addition, when comparing the full potential of the VAT reduction in the restaurant sector, it had not been applied as planned. Restaurants reacted differently to the VAT reduction. The restaurants selected for the study can be divided into different categories, based on how they changed the pricing of their products. The questionnaire was sent to 1469 students, out of which 204 responses were received. Thus, the response rate was 14. The results of the survey indicated that the VAT reduction did not affect consumer behavior. From the consumer point of view, the VAT reduction was not realized as planned. The thesis can be used as a basic research material in the future, and it was current because the VAT reduction is expected to revive the restaurant sector and increase consumption