Browsing by Subject "HYPERTENSION"

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  • Zhou, Wei; Brumpton, Ben; Kabil, Omer; Gudmundsson, Julius; Thorleifsson, Gudmar; Weinstock, Josh; Zawistowski, Matthew; Nielsen, Jonas B.; Chaker, Layal; Medici, Marco; Teumer, Alexander; Naitza, Silvia; Sanna, Serena; Schultheiss, Ulla T.; Cappola, Anne; Karjalainen, Juha; Kurki, Mitja; Oneka, Morgan; Taylor, Peter; Fritsche, Lars G.; Graham, Sarah E.; Wolford, Brooke N.; Overton, William; Rasheed, Humaira; Haug, Eirin B.; Gabrielsen, Maiken E.; Skogholt, Anne Heidi; Surakka, Ida; Smith, George Davey; Pandit, Anita; Roychowdhury, Tanmoy; Hornsby, Whitney E.; Jonasson, Jon G.; Senter, Leigha; Liyanarachchi, Sandya; Ringel, Matthew D.; Xu, Li; Kiemeney, Lambertus A.; He, Huiling; Netea-Maier, Romana T.; Mayordomo, Jose; Plantinga, Theo S.; Hrafnkelsson, Jon; Hjartarson, Hannes; Sturgis, Erich M.; Palotie, Aarno; Daly, Mark; Citterio, Cintia E.; Arvan, Peter; Brummett, Chad M.; Boehnke, Michael; de la Chapelle, Albert; Stefansson, Kari; Hveem, Kristian; Willer, Cristen J.; Asvold, Bjorn Olav (2020)
    Thyroid stimulating hormone (TSH) is critical for normal development and metabolism. To better understand the genetic contribution to TSH levels, we conduct a GWAS meta-analysis at 22.4 million genetic markers in up to 119,715 individuals and identify 74 genome-wide significant loci for TSH, of which 28 are previously unreported. Functional experiments show that the thyroglobulin protein-altering variants P118L and G67S impact thyroglobulin secretion. Phenome-wide association analysis in the UK Biobank demonstrates the pleiotropic effects of TSH-associated variants and a polygenic score for higher TSH levels is associated with a reduced risk of thyroid cancer in the UK Biobank and three other independent studies. Two-sample Mendelian randomization using TSH index variants as instrumental variables suggests a protective effect of higher TSH levels (indicating lower thyroid function) on risk of thyroid cancer and goiter. Our findings highlight the pleiotropic effects of TSH-associated variants on thyroid function and growth of malignant and benign thyroid tumors. Thyroid stimulating hormone (TSH) is critical for normal development and metabolism. Here, the authors conduct a GWAS and suggest protective effect of higher TSH on risk of thyroid cancer and goitre.
  • Zhou, Ang; Taylor, Amy E.; Karhunen, Ville; Zhan, Yiqiang; Rovio, Suvi P.; Lahti, Jari; Sjögren, Per; Byberg, Liisa; Lyall, Donald M.; Auvinen, Juha; Lehtimaki, Terho; Kahonen, Mika; Hutri-Kahonen, Nina; Perala, Mia Maria; Michaelsson, Karl; Mahajan, Anubha; Lind, Lars; Power, Chris; Eriksson, Johan G.; Raitakari, Olli T.; Hagg, Sara; Pedersen, Nancy L.; Veijola, Juha; Jarvelin, Marjo-Riitta; Munafo, Marcus R.; Ingelsson, Erik; Llewellyn, David J.; Hypponen, Elina (2018)
    Coffee's long-term effect on cognitive function remains unclear with studies suggesting both benefits and adverse effects. We used Mendelian randomization to investigate the causal relationship between habitual coffee consumption and cognitive function in mid-to later life. This included up to 415,530 participants and 300,760 coffee drinkers from 10 meta-analysed European ancestry cohorts. In each cohort, composite cognitive scores that capture global cognition and memory were computed using available tests. A genetic score derived using CYP1A1/2 (rs2472297) and AHR (rs6968865) was chosen as a proxy for habitual coffee consumption. Null associations were observed when examining the associations of the genetic score with global and memory cognition (beta = -0.0007, 95% C.I. -0.009 to 0.008, P = 0.87; beta = -0.001, 95% C.I. -0.005 to 0.002, P = 0.51, respectively), with high consistency between studies (P-heterogeneity > 0.4 for both). Domain specific analyses using available cognitive measures in the UK Biobank also did not support effects by habitual coffee intake for reaction time, pairs matching, reasoning or prospective memory (P >= 0.05 for all). Despite the power to detect very small effects, our meta-analysis provided no evidence for causal long-term effects of habitual coffee consumption on global cognition or memory.
  • Mellembakken, Jan Roar; Mahmoudan, Azita; Morkrid, Lars; Sundström-Poromaa, Inger; Morin-Papunen, Laure; Tapanainen, Juha S.; Piltonen, Terhi T.; Hirschberg, Angelica Linden; Stener-Victorin, Elisabet; Vanky, Eszter; Ravn, Pernille; Jensen, Richard Christian; Andersen, Marianne Skovsager; Glintborg, Dorte (2021)
    Objective: Obesity is considered to be the strongest predictive factor for cardio-metabolic risk in women with polycystic ovary syndrome (PCOS). The aim of the study was to compare blood pressure (BP) in normal weight women with PCOS and controls matched for age and BMI. Methods: From a Nordic cross-sectional base of 2615 individuals of Nordic ethnicity, we studied a sub cohort of 793 normal weight women with BMI <25 k g/m(2) (512 women with PCOS according to Rotterdam criteria and 281 age and BMI-matched controls). Participants underwent measurement of BP and body composition (BMI, waist-hip ratio), lipid status, and fasting BG. Data were presented as median (quartiles). Results: The median age for women with PCOS were 28 (25, 32) years and median BMI was 22.2 (20.7, 23.4) kg/m(2). Systolic BP was 118 (109, 128) mmHg in women with PCOS compared to 110 (105, 120) mmHg in controls and diastolic BP was 74 ( 67, 81) vs 70 (64, 75) mmHg, both P <0.001. The prevalence of women with BP >= 140/90 mmHg was 11.1% (57/ 512) in women with PCOS vs 1.8% (5/281) in controls, P <0.001. In women >= 35 years the prevalence of BP >= 140/90 mmHg was comparable in women with PCOS and controls (12.7% vs 9.8%, P = 0.6). Using multiple regression analyses, the strongest association with BP was found for age, waist circumference, and total cholesterol in women with PCOS. Conclusions: Normal weight women with PCOS have higher BP than controls. BP and metabolic screening are relevant also in young normal weight women with PCOS.
  • Gaal, Emilia Ilona; Salo, Perttu; Kristiansson, Kati; Rehnstrom, Karola; Kettunen, Johannes; Sarin, Antti-Pekka; Niemela, Mika; Jula, Antti; Raitakari, Olli T.; Lehtimaki, Terho; Eriksson, Johan G.; Widen, Elisabeth; Guenel, Murat; Kurki, Mitja; Fraunberg, Mikael von Und Zu; Jaaskelainen, Juha E.; Hernesniemi, Juha; Jarvelin, Marjo-Riitta; Pouta, Anneli; Newton-Cheh, Christopher; Salomaa, Veikko; Palotie, Aarno; Perola, Markus; ICBP-GWAS (2012)
  • Korhonen, Maarit J.; Pentti, Jaana; Hartikainen, Juha; Ilomaki, Jenni; Setoguchi, Soko; Liew, Danny; Kivimäki, Mika; Vahtera, Jussi (2020)
    Background--Lifestyle modification is a key component of cardiovascular disease prevention before and concurrently with pharmacologic interventions. We evaluated whether lifestyle factors change in relation to the initiation of antihypertensive or lipidlowering medication (statins). Methods and Results--The study population comprised 41 225 participants of the FPS (Finnish Public Sector) study aged =40 years who were free of cardiovascular disease at baseline and responded to =2 consecutive surveys administered in 4-year intervals in 2000-2013. Medication use was ascertained through pharmacy-claims data. Using a series of pre-post data sets, we compared changes in body mass index, physical activity, alcohol consumption, and smoking between 8837 initiators and 46 021 noninitiators of antihypertensive medications or statins. In participants who initiated medication use, body mass index increased more (difference in change 0.19; 95% CI, 0.16-0.22) and physical activity declined (-0.09 metabolic equivalent of task hour/day; 95% CI, -0.16 to -0.02) compared with noninitiators. The likelihood of becoming obese (odds ratio: 1.82; 95% CI, 1.63-2.03) and physically inactive (odds ratio: 1.08; 95% CI, 1.01-1.17) was higher in initiators. However, medication initiation was associated with greater decline in average alcohol consumption (-1.85 g/week; 95% CI, -3.67 to -0.14) and higher odds of quitting smoking (odds ratio for current smoking in the second survey: 0.74; 95% CI, 0.64-0.85). Conclusions--These findings suggest that initiation of antihypertensive and statin medication is associated with lifestyle changes, some favorable and others unfavorable. Weight management and physical activity should be encouraged in individuals prescribed these medications.
  • Virtanen, Marianna; Kivimäki, Mika (2018)
    To summarize the evidence on the relationship between long working hours and cardiovascular disease, such as coronary heart disease and stroke. Large-scale meta-analyses with published and individual participant observational data on more than 740,000 men and women free of cardiovascular disease report a link between long working hours (>= 55 h a week) and the onset of cardiovascular events. Our meta-analytic update of summary evidence suggests a 1.12-fold (95% CI 1.03-1.21) increased risk associated with coronary heart disease and a 1.21-fold (95% CI 1.01-1.45) increased risk of stroke, although the evidence is somewhat inconsistent and the possibility of residual confounding and bias cannot be ruled out. Few studies have examined the mechanisms which may be stress-related, behavioral, or biological. The recent pooled analyses suggest that increased cardiac electric instability and hypercoagulability might play a role. The evidence that long working hours are a risk factor for cardiovascular disease is accumulating and suggests a small risk. Studies on the effects of long working hours in high-risk populations and those with pre-existing cardiovascular disease, mechanistic research, and intervention studies are needed to advance this research field.
  • Virtanen, Marianna; Hansson, Linda Magnusson; Goldberg, Marcel; Zins, Marie; Stenholm, Sari; Vahtera, Jussi; Westerlund, Hugo; Kivimäki, Mika (2019)
    Background Although long working hours have been shown to be associated with the onset of cardiometabolic diseases, the clinical risk factor profile associated with long working hours remains unclear. We compared the clinical risk profile between people who worked long hours and those who reported being never exposed to long hours. Methods A cross-sectional study in 22 health screening centres in France was based on a random population-based sample of 75 709 participants aged 18-69 at study inception in 2012-2016 (the CONSTANCES study). The data included survey responses on working hours (never, former or current exposure to long working hours), covariates and standardised biomedical examinations including anthropometry, lung function, blood pressure and standard blood-based biomarkers. Results Among men, long working hours were associated with higher anthropometric markers (Body Mass Index, waist circumference and waist:hip ratio), adverse lipid levels, higher glucose, creatinine, white blood cells and higher alanine transaminase (adjusted mean differences in the standardised scale between the exposed and unexposed 0.02-0.12). The largest differences were found for Body Mass Index and waist circumference. A dose-response pattern with increasing years of working long hours was found for anthropometric markers, total cholesterol, glucose and gamma-glutamyltransferase. Among women, long working hours were associated with Body Mass Index and white blood cells. Conclusion In this study, men who worked long hours had slightly worse cardiometabolic and inflammatory profile than those who did not work long hours, especially with regard to anthropometric markers. In women, the corresponding associations were weak or absent.
  • Smith, Erin N.; Chen, Wei; Kahonen, Mika; Kettunen, Johannes; Lehtimaki, Terho; Palotie, Leena; Raitakari, Olli T.; Salem, Rany M.; Schork, Nicholas J.; Shaw, Marian; Srinivasan, Sathanur R.; Topol, Eric J.; Viikari, Jorma S.; Berenson, Gerald S.; Murray, Sarah S. (2010)
  • Kaseva, Nina; Wehkalampi, Karoliina; Strang-Karlsson, Sonja; Salonen, Minna; Pesonen, Anu-Katriina; Räikkönen, Katri; Tammelin, Tuija; Hovi, Petteri; Lahti, Jari; Heinonen, Kati; Jarvenpaa, Anna-Liisa; Andersson, Sture; Eriksson, Johan G.; Kajantie, Eero (2012)
  • Bono, Petri; Oudard, Stephane; Bodrogi, Istvan; Hutson, Thomas E.; Escudier, Bernard; Machiels, Jean-Pascal; Thompson, John A.; Figlin, Robert A.; Ravaud, Alain; Basaran, Mert; Porta, Camillo; Bracarda, Sergio; Brechenmacher, Thomas; Lin, Chinjune; Voi, Maurizio; Grunwald, Viktor; Motzer, Robert J. (2016)
    In this study we examined the outcome of metastatic renal cell cancer patients with everolimus treatment related hyperglycemia and hypercholesterolemia. All patients were treated in 2 large, international prospective trials, RECORD-1 (REnal Cell cancer treatment with Oral RADOO1 given Daily) and REACT (RADOO1 Expanded Access Clinical Trial in RCC). Patients who experienced these events might have experienced an improved response to everolimus. Background: Hyperglycemia and hypercholesterolemia are class effects of mammalian target of rapamycin inhibitors. The purpose of this study was to characterize safety and efficacy of patients with metastatic renal cell carcinoma (mRCC) treated with everolimus in RECORD-1 (REnal Cell cancer treatment with Oral RAD001 given Daily) and REACT (RAD001 Expanded Access Clinical Trial in RCC) who developed these events. Patients and Methods: Adults with vascular endothelial growth factor refractory mRCC received everolimus 10 mg/d in the randomized RECORD-1 (n = 277) and open-label REACT (n = 1367) studies. Outcomes included safety, treatment duration, overall response, and progression free survival for patients who developed hypercholesterolemia or hyperglycemia. Results: In RECORD-1, 12% (33 of 277) and 20% (55 of 277) of patients developed any grade hyperglycemia or hypercholesterolemia, respectively, with only 6% (78 of 1367) and 1% (14 of 1367) of the same events, respectively, in REACT. Median everolimus treatment duration was similar for patients with hyperglycemia or hypercholesterolemia (RECORD-1, 6.2 and 6.2 months, respectively; REACT, 4.4 and 4.5 months, respectively), but longer-than the overall populations (RECORD-1, 4.6 months; REACT, 3.2 months). In RECORD-1/REACT, 82%/68% of patients with hyperglycemia and 75%/71% of patients with hypercholesterolemia achieved partial response or stable disease. The incidence of clinically notable Grade 3 or 4 adverse events, other than anemia and lymphopenia, appeared to be similar across trials and subgroups. Although there was a trend for improved progression-free survival with development of hyperglycemia or hypercholesterolemia, the association was not statistically significant. Conclusion: Hyperglycemia and hypercholesterolemia were observed in low numbers of patients, and although these events might be associated with improved response to everolimus, the differences were not significant. These findings should be validated with prospective biomarker studies.
  • Vainio, Tuomas J V; Mäkelä, Teemu Olavi; Savolainen, Sauli; Kangasniemi, Marko Matti (2021)
    Background Chronic pulmonary embolism (CPE) is a life-threatening disease easily misdiagnosed on computed tomography. We investigated a three-dimensional convolutional neural network (CNN) algorithm for detecting hypoperfusion in CPE from computed tomography pulmonary angiography (CTPA). Methods Preoperative CTPA of 25 patients with CPE and 25 without pulmonary embolism were selected. We applied a 48%-12%-40% training-validation-testing split (12 positive and 12 negative CTPA volumes for training, 3 positives and 3 negatives for validation, 10 positives and 10 negatives for testing). The median number of axial images per CTPA was 335 (min-max, 111-570). Expert manual segmentations were used as training and testing targets. The CNN output was compared to a method in which a Hounsfield unit (HU) threshold was used to detect hypoperfusion. Receiver operating characteristic area under the curve (AUC) and Matthew correlation coefficient (MCC) were calculated with their 95% confidence interval (CI). Results The predicted segmentations of CNN showed AUC 0.87 (95% CI 0.82-0.91), those of HU-threshold method 0.79 (95% CI 0.74-0.84). The optimal global threshold values were CNN output probability >= 0.37 and
  • Niini, Tarmo; Laakso, Aki; Tanskanen, Päivi; Niemelä, Mika; Luostarinen, Teemu (2019)
    We reviewed retrospectively the perioperative treatment of microsurgically resected brain arteriovenous malformations (bAVMs) at the neurosurgical department of Helsinki University Hospital between the years 2006 and 2014. We examined the performance of the treatment protocol and the incidence of delayed postoperative hemorrhage (DPH).
  • Huhtakangas, Juha; Lopponen, Pekka; Tetri, Sami; Juvela, Seppo; Saloheimo, Pertti; Bode, Michaela K.; Hillbom, Matti (2013)
  • Eriksson, Johan G.; Salonen, Minna K.; Kajantie, Eero; Osmond, Clive (2018)
    Background: According to the Developmental Origins of Health and Disease (DOHaD) hypothesis, several noncommunicable diseases, including hypertension, type 2 diabetes, and coronary heart disease, have their origins in early life. Chronic kidney disease (CKD) has traditionally been assumed to develop as the result of an interaction between genetic and environmental factors, although more recently, the importance of factors present early in life has been recognized. Study Design: Longitudinal birth cohort study. Setting & Participants: 20,431 people born in 1924 to 1944 in Helsinki, Finland, who were part of the Helsinki Birth Cohort Study were followed up through their life course from birth until death or age 86 years. Predictor: Prenatal growth and socioeconomic factors. Outcomes: Death or hospitalization for CKD. Results: Smaller body size at birth was associated with increased risk for developing CKD. Each standard deviation higher birth weight was associated with an HR for CKD of 0.82 (95% CI, 0.74-0.91; P <0.001). Associations with ponderal index at birth, placental weight, and birth length were also statistically significant (P <0.001, P <0.001, and P = 0.002, respectively), but only among men. Prematurity also predicted increased risk for CKD. Limitations: The study was restricted to people who were born in Helsinki in 1924 to 1944. Conclusions: Smaller body size at birth was associated with increased risk for developing CKD in men. Prematurity was also associated with increased risk for CKD in women. These findings in the Helsinki Birth Cohort Study support the importance of early life factors in the development of CKD.
  • Luta, X.; Hayoz, S.; Krause, C. Grea; Sommerhalder, K.; Roos, E.; Strazzullo, P.; Beer-Borst, S. (2018)
    Background and aims: High sodium (Na) and low potassium (K) intake are associated with hypertension and CVD risk. This study explored the associations of health literacy (HL), food literacy (FL), and salt awareness with salt intake, K intake, and Na/K ratio in a workplace intervention trial in Switzerland. Methods and results: The study acquired baseline data from 141 individuals, mean age 44.6 years. Na and K intake were estimated from a single 24-h urine collection. We applied validated instruments to assess HL and FL, and salt awareness. Multiple linear regression was used to investigate the association of explanatory variables with salt intake, K intake, and Na/K. Mean daily salt intake was 8.9 g, K 3.1 g, and Na/K 1.18. Salt intake was associated with sex (p <0.001), and K intake with sex (p <0.001), age (p = 0.02), and waist-to-height ratio (p = 0.03), as was Na/K. HL index and FL score were not significantly associated with salt or K intake but the awareness variable "salt content impacts food/menu choice" was associated with salt intake (p = 0.005). Conclusion: To achieve the established targets for population Na and K intake, health-related knowledge, abilities, and skills related to Na/salt and K intake need to be promoted through combined educational and structural interventions. (C) 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V.
  • Törmänen, Suvi; Lakkisto, Päivi; Eräranta, Arttu; Kööbi, Peeter; Tikkanen, Ilkka; Niemelä, Onni; Mustonen, Jukka; Pörsti, Ilkka (2020)
    Chronic renal insufficiency (CRI) is characterized by increased endothelin 1 (ET-1) synthesis. We studied rat kidney endothelin receptor A (ETA) and receptor B (ETB) expressions after 12 and 27 weeks of 5/6 nephrectomy, and after 12 weeks of 0.3% adenine diet, representing proteinuric and interstitial inflammation models of CRI, respectively. Uric acid and calcium-phosphate metabolism were modulated after 5/6 nephrectomy, while ETA blocker and calcimimetic were given with adenine. Endothelin receptor mRNA levels were measured using RT-qPCR and protein levels using autoradiography (5/6 nephrectomy) or ELISA (adenine model). Both 12 and 27 weeks after 5/6 nephrectomy, kidney cortex ETA protein was increased by similar to 60% without changes in ETB protein, and the ETB:ETA ratio was reduced. However, the ETB:ETA mRNA ratio did not change. In the adenine model, kidney ETA protein was reduced by similar to 70%, while ETB protein was suppressed by similar to 95%, and the ETB:ETA ratio was reduced by similar to 85%, both at the protein and mRNA levels. The additional interventions did not influence the observed reductions in the ETB:ETAratio. To conclude, unfavorable reduction in the ETB:ETA protein ratio was observed in two different models of CRI. Therefore, ETA blockade may be beneficial in a range of diseases that cause impaired kidney function.
  • Laurila, Henna P.; Rajamäki, Minna M. (2020)
    Canine idiopathic pulmonary fibrosis (CIPF) is a chronic, progressive, interstitial lung disease (ILD) affecting older West Highland white terriers (WHWTs). According to one classification, CIPF is a familial fibrotic ILD in the group of idiopathic interstitial pneumonias. Etiology is unknown but likely arises from interplay between genetic and environmental factors. CIPF shares features with human idiopathic pulmonary fibrosis and human nonspecific interstitial pneumonia. This article describes clinical signs, findings in physical examination, arterial oxygenation, diagnostic imaging, bronchoscopy, bronchoalveolar lavage, histopathology, disease course, and outcome of WHWTs with CIPF; compares canine and human diseases; summarizes biomarker research; and gives an overview of potential treatment.
  • Bajc, Marika; Lindqvist, Ari (2019)
    Ventilation/perfusion single-photon emission computed tomography (V/P SPECT) is the scintigraphic technique recommended primarily for the diagnosis of acute pulmonary embolism (PE) and is golden standard for the diagnosis of chronic PE. Furthermore, interpreting ventilation and corresponding perfusion images enables pattern recognition of many other cardiopulmonary disorders that affect lung function and also allows quantification of their extent. Using Technegas for the ventilation imaging, grading of small airway disease in COPD is possible and the method is recommended for PE diagnosis in patients with severe COPD that is not possible with radiolabelled liquid aerosols. An optimal combination of nuclide activities, acquisition times for ventilation and perfusion, collimators, and imaging matrix yields an adequate V/P SPECT study in approximately 20 minutes of imaging time. The holistic interpretation strategy of V/P SPECT uses all relevant information about the patient and ventilation/ perfusion patterns. PE is diagnosed when there is more than one subsegment showing a V/P mismatch representing an anatomic lung unit. Apart from PE, other pathologies should be identified and reported, such as obstructive lung disease, heart failure, and pneumonia according to the European Association of Nuclear Medicine guidelines. Semin Nucl Med 49:4-10 (C) 2018 Published by Elsevier Inc.