Browsing by Subject "BLOOD-PRESSURE"

Sort by: Order: Results:

Now showing items 1-20 of 108
  • Saviluoto, Anssi; Harve-Rytsälä, Heini; Lääperi, Mitja; Kirves, Hetti; Jantti, Helena; Nurmi, Jouni (2020)
    Background Identifying stroke and other intracranial lesions in patients with a decreased level of consciousness may be challenging in prehospital settings. Our objective was to investigate whether the combination of systolic blood pressure, heart rate and age could be used to identify intracranial lesions. Methods We conducted a retrospective case-control study including patients with a decreased level of consciousness who had their airway secured during prehospital care. Patients with intracranial lesions were identified based on the final diagnoses at the end of hospitalization. We investigated the ability of systolic blood pressure, heart rate and age to identify intracranial lesions and derived a decision instrument. Results Of 425 patients, 127 had an intracranial lesion. Patients with a lesion were characterized by higher systolic blood pressure, lower heart rate and higher age (P <0.0001 for all). A systolic blood pressure >= 140 mmHg had an odds ratio (OR) of 3.5 (95% confidence interval [CI] 1.7 to 7.0), and > 170 mmHg had an OR of 8.2 (95% CI 4.5-15.32) for an intracranial lesion (reference: <140 mmHg). A heart rate <100 beats/min had an OR of 3.4 (95% CI 2.0 to 6.0, reference: >= 100). Age 50-70 had an OR of 4.1 (95% CI 2.0 to 9.0), and > 70 years had an OR of 10.2 (95% CI 4.8 to 23.2), reference: <50. Logarithms of ORs were rounded to the nearest integer to create a score with 0-2 points for age and blood pressure and 0-1 for heart rate, with an increasing risk for an intracranial lesion with higher scores. The area under the receiver operating characteristics curve for the instrument was 0.810 (95% CI 0.850-0.890). Conclusions An instrument combining systolic blood pressure, heart rate and age may help identify stroke and other intracranial lesions in patients with a decreased level of consciousness in prehospital settings.
  • Eriksson, Johan G.; Salonen, Minna K.; von Bonsdorff, Mikaela B.; Wasenius, Niko; Kajantie, Eero; Kautiainen, Hannu; Mikkola, Tuija M. (2022)
    The main objective of this study was to study predictors of vascular health with focus on adiposity-related factors. Glucose metabolism, blood lipids, inflammatory markers and body composition were assessed 15 years before assessment of vascular health which was assessed with pulse wave velocity (PWV) in 660 subjects born 1934-44. In a univariate analysis in women the strongest association with PWV was seen for age, systolic blood pressure, dysglycemia, dyslipidemia, inflammatory markers and body fat percentage measured in late midlife and PWV measured 15 years later. In men age, body mass index (BMI), systolic blood pressure, dysglycemia, and body fat percentage in late midlife were associated with PWV. One novel finding was that adiposity-related factors were strong predictors of vascular health, something not fully encapsulated in BMI, lean body mass or body fat percentage alone. A higher fat mass index was associated with worse vascular health, which was not ameliorated by a higher lean mass index. Our findings stress the importance to study body composition and fat and lean body mass simultaneously because of their close interaction with each other also in relation to vascular health.
  • Bennet, Louise; Nilsson, Christopher; Mansour-Aly, Dina; Christensson, Anders; Groop, Leif; Ahlqvist, Emma (2021)
    Background Middle Eastern immigrants to Europe represent a high risk population for type 2 diabetes. We compared prevalence of novel subgroups and assessed risk of diabetic macro- and microvascular complications between diabetes patients of Middle Eastern and European origin. Methods This study included newly diagnosed diabetes patients born in Sweden (N = 10641) or Iraq (N = 286), previously included in the All New Diabetes in Scania cohort. The study was conducted between January 2008 and August 2016. Patients were followed to April 2017. Incidence rates in diabetic macro- and microvascular complications were assessed using cox-regression adjusting for the confounding effect of age at onset, sex, anthropometrics, glomerular filtration rate (eGFR) and HbA1c. Findings In Iraqi immigrants versus native Swedes, severe insulin-deficient diabetes was almost twice as common (27.9 vs. 16.2% p <0.001) but severe insulin-resistant diabetes was less prevalent. Patients born in Iraq had higher risk of coronary events (hazard ratio [HR] 1.84, 95% CI 1.06-3.12) but considerably lower risk of chronic kidney disease (CKD) than Swedes (HR 0.19; 0.05-0.76). The lower risk in Iraqi immigrants was partially attributed to better eGFR. Genetic risk scores (GRS) showed more genetic variants associated with poor insulin secretion but lower risk of insulin resistance in the Iraqi than native Swedish group. Interpretation People with diabetes, born in the Middle East present with a more insulin-deficient phenotype and genotype than native Swedes. They have a higher risk of coronary events but lower risk of CKD. Ethnic differences should be considered in the preventive work towards diabetes and its complications.
  • Kokko, Eeva; Nevalainen, Pasi; Choudhary, Manoj Kumar; Koskela, Jenni; Tikkakoski, Antti; Huhtala, Heini; Niemelä, Onni; Viukari, Marianna; Mustonen, Jukka; Matikainen, Niina; Pörsti, Ilkka (2020)
    Aldosterone-to-renin ratio (ARR) is a screening tool for primary aldosteronism (PA), but the significance of ARR when the PA criteria are not met remains largely unknown. In this cross-sectional study we investigated the association of ARR with haemodynamic variables in 545 normotensive and never-medicated hypertensive subjects (267 men, 278 women, age range 19-72 years) without suspicion of PA. Supine haemodynamic data was recorded using whole-body impedance cardiography and radial tonometric pulse wave analysis. In sex-adjusted quartiles of ARR, determined as serum aldosterone to plasma renin activity ratio, the mean values were 282, 504, 744 and 1467 pmol/mu g of angiotensin I/h, respectively. The only difference in haemodynamic variables between the ARR quartiles was higher pulse wave velocity (PWV) in the highest quartile versus other quartiles (p=0.004), while no differences in blood pressure (BP), heart rate, wave reflections, cardiac output or systemic vascular resistance were observed between the quartiles. In linear regression analysis with stepwise elimination, ARR was an independent explanatory factor for PWV (beta =0.146, p
  • Wehkalampi, Karoliina; Muurinen, Mari; Wirta, Sara Bruce; Hannula-Jouppi, Katariina; Hovi, Petteri; Järvenpää, Anna-Liisa; Eriksson, Johan G.; Andersson, Sture; Kere, Juha; Kajantie, Eero (2013)
  • Benetos, Athanase; Bulpitt, Christopher J.; Petrovic, Mirko; Ungar, Andrea; Rosei, Enrico Agabiti; Cherubini, Antonio; Redon, Josep; Grodzicki, Tomasz; Dominiczak, Anna; Strandberg, Timo; Mancia, Giuseppe (2016)
  • Karppanen, Tiina; Kaartokallio, Tea; Klemetti, Miira M.; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli; Staff, Anne Cathrine; Laivuori, Hannele (2016)
    Background: Preeclampsia is a common and heterogeneous vascular syndrome of pregnancy. Its genetic risk profile is yet unknown and may vary between individuals and populations. The rs4606 3'UTR polymorphism of the Regulator of G-protein signaling 2 gene (RGS2) in the mother has been implicated in preeclampsia as well as in the development of chronic hypertension after preeclampsia. The RGS2 protein acts as an inhibitor of physiological vasoconstrictive pathways, and a low RGS2 level is associated with hypertension and obesity, two conditions that predispose to preeclampsia. We genotyped the rs4606 polymorphism in 1339 preeclamptic patients and in 697 controls from the Finnish Genetics of Preeclampsia Consortium (FINNPEC) cohort to study the association of the variant with preeclampsia. Results: No association between rs4606 and preeclampsia was detected in the analysis including all women. However, the polymorphism was associated with preeclampsia in a subgroup of overweight women (body mass index >= 25 kg/m(2), and <30 kg/m(2)) (dominant model; odds ratio, 1.64; 95 % confidence interval, 1.10-2.42). Conclusions: Our results suggest that RGS2 might be involved in the pathogenesis of preeclampsia particularly in overweight women and contribute to their increased risk for hypertension and other types of cardiovascular disease later in life.
  • Korkalainen, Noora; Mäkikallio, Timo; Räsänen, Juha; Huikuri, Heikki; Mäkikallio, Kaarin (2021)
    Background: According to epidemiological studies, impaired intrauterine growth increases the risk for cardiovascular morbidity and mortality in adulthood. Heart rate variability (HRV), which reflects the autonomic nervous system function, has been used for risk assessment in adults while its dysfunction has been linked to poor cardiovascular outcome. Objective: We hypothesized that children who were born with fetal growth restriction (FGR) and antenatal blood flow redistribution have decreased HRV at early school age compared to their gestational age matched peers with normal intrauterine growth. Study design: A prospectively collected cohort of children born with FGR (birth weight = -2SD. Conclusions: Early school age children born with FGR and intrauterine blood flow redistribution demonstrated altered heart rate variability. These prenatal and postnatal findings may be helpful in targeting preventive cardiovascular measures in FGR.
  • Tynjälä, Anniina; Forsblom, Carol; Harjutsalo, Valma; Groop, Per-Henrik; Gordin, Daniel (2020)
    OBJECTIVE Type 1 diabetes is accompanied by a significant burden of cardiovascular disease (CVD), which is poorly explained by traditional risk factors. We therefore aimed to explore whether arterial stiffness estimated by the augmentation index (AIx) predicts mortality in individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS After baseline examination comprising pulse wave analysis by applanation tonometry alongside assessment of traditional cardiovascular risk factors, 906 individuals with type 1 diabetes from the Finnish Diabetic Nephropathy (FinnDiane) Study were followed up for a median of 8.2 years (interquartile range 5.7-9.7). Associations between baseline hemodynamics, including AIx, and all-cause mortality as well as a composite of cardiovascular and/or diabetes-related mortality were investigated using multivariable Cox regression models. RESULTS The 67 individuals who died during follow-up had higher baseline AIx (median 28% [interquartile range 21-33] vs. 19% [9-27];P<0.001) compared with those alive. This association was independent of conventional risk factors (age, sex, BMI, HbA(1c), estimated glomerular filtration rate [eGFR], and previous CVD event) in Cox regression analysis (standardized hazard ratio 1.71 [95% CI 1.10-2.65];P= 0.017) and sustained in a subanalysis of individuals with chronic kidney disease. Similarly, higher AIx was associated with the composite secondary end point of cardiovascular and diabetes-related death (N= 53) after adjustments for sex, BMI, eGFR, previous CVD event, and height (standardized hazard ratio 2.30 [1.38-3.83];P= 0.001). CONCLUSIONS AIx predicts all-cause mortality as well as a composite cardiovascular and/or diabetes-related cause of death in individuals with type 1 diabetes, independent of established cardiovascular risk factors.
  • Åberg, Fredrik; Kantojärvi, Katri; Männistö, Ville; But, Anna; Salomaa, Veikko; Niiranen, Teemu; Färkkilä, Martti; Luukkonen, Panu; Männistö, Satu; Lundqvist, Annamari; Perola, Markus; Jula, Antti (2022)
    Arterial hypertension (HTA) is associated with liver disease, but causality remains unclear. We investigated whether genetic predisposition to HTA is associated with liver disease in the population, and if antihypertensive medication modifies this association. Participants of the Finnish health-examination surveys, FINRISK 1992-2012 and Health 2000 (n = 33,770), were linked with national electronic healthcare registers for liver-related outcomes (K70-K77, C22.0) and with the drug reimbursement registry for new initiation of antihypertensive medication during follow-up. Genetic predisposition to HTA was defined by polygenic risk scores (PRSs). During a median 12.9-year follow-up (409,268.9 person-years), 441 liver-related outcomes occurred. In the fully-adjusted Cox-regression models, both measured systolic blood pressure and clinically defined HTA were associated with liver-related outcomes. PRSs for systolic and diastolic blood pressure were significantly associated with liver-related outcomes (HR/SD 1.19, 95% CI 1.01-1.24, and 1.12, 95% CI 1.01-1.25, respectively). In the highest quintile of the systolic blood pressure PRS, new initiation of antihypertensive medication was associated with reduced rates of liver-related outcomes (HR 0.55, 95% CI 0.31-0.97). HTA and a genetic predisposition for HTA are associated with liver-related outcomes in the population. New initiation of antihypertensive medication attenuates this association in persons with high genetic risk for HTA.
  • FinnDiane Study Grp (2018)
    Background and aims: Increased arterial stiffness contributes to diabetic vascular complications. We identified dietary factors related to arterial stiffness in individuals with type 1 diabetes, a population with high risk of cardiovascular disease. Methods and results: Altogether, 612 participants (40% men, mean +/- standard deviation age 45 +/- 13 years) completed a validated diet questionnaire and underwent measurements of arterial stiffness. Of these, 470 additionally completed a food record. Exploratory factor analysis was applied to identify dietary patterns from the diet questionnaires, and nutrient intakes were calculated from food record entries. Arterial stiffness was measured by applanation tonometry. Of the seven dietary factors formed, the factor scores of "Full-fat cheese and eggs" and "Sweet" patterns were negatively associated with measures of arterial stiffness. In the multivariable macronutrient substitution models, favouring carbohydrates over fats was associated with higher aortic mean arterial pressure and aortic pulse wave velocity. When carbohydrates were consumed in place of proteins, higher aortic pulse pressure, aortic mean arterial pressure, and augmentation index were recorded. Replacing energy from alcohol with proteins, was associated with lower aortic pulse pressure, aortic mean arterial pressure, and augmentation index. Relative distributions of dietary fatty acids were neutral with respect to the measures of arterial stiffness. Conclusion: The macronutrient distribution of the diet is likely to affect the resilience of the arteries. Our observations suggest that reducing energy intake from carbohydrates and alcohol may be beneficial. These observations, especially those dealing with dietary patterns, need to be confirmed in a longitudinal study. (C) 2018 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. All rights reserved.
  • Smith, Drew H.; Grewal, Jaskaran; Mehboob, Saba; Mohan, Shiva; Pombo, Luisa F.; Rodriguez, Pura; Gonzalez, Juan Carlos; Zevallos, Juan; Barengo, Noel C. (2022)
    Background Studies in the United States have shown a genetic predisposition to hypertension in individuals of African descent. However, studies on the associations between ethnic groups and hypertension in Latin America are lacking and the limited results have been inconsistent. The objective of this study is to determine whether Afro-Colombian ethnicity increases the risk of hypertension. Methods This study is a secondary data analysis of a cross sectional study from five provinces in Northern Colombia. Randomly selected individuals (N = 2613; age-range 18-74 years) enrolled in a health care insurance company underwent physical examinations and completed questionnaires regarding ethnicity, lifestyle, and other risk factors. Hypertension in these patients was determined. Unadjusted and adjusted logistic regression analysis were calculated to determine the association between ethnicity and hypertension. Results No association between Afro-Colombian ethnicity and hypertension was found (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.66-1.09). As expected, people with a body mass index (BMI) of 30 or higher were at a greater risk of having hypertension (OR, 3.12; 95% CI, 2.35-4.16) compared with those with a normal BMI. Conclusions Findings from this study suggest no independent association between Afro-Colombian ethnicity and hypertension. Further research should focus on genotyping or socioeconomic factors such as income level.
  • Pihlman, Jukka; Magnussen, Costan G.; Rovio, Suvi P.; Pahkala, Katja; Jokinen, Eero; Laitinen, Tomi P.; Hutri-Kahonen, Nina; Tossavainen, Paivi; Taittonen, Leena; Kahonen, Mika; Viikari, Jorma S. A.; Raitakari, Olli T.; Juonala, Markus; Nuotio, Joel (2021)
    Objective To determine the association of number of siblings on cardiovascular risk factors in childhood and in adulthood. Study design In total, 3554 participants (51% female) from the Cardiovascular Risk in Young Finns Study with cardiovascular disease risk factor data at baseline 1980 (age 3-18 years) and 2491 participants with longitudinal risk factor data at the 2011 follow-up. Participants were categorized by number of siblings at baseline (0, 1, or more than 1). Risk factors (body mass index, physical activity, hypertension, dyslipidemia, and overweight, and metabolic syndrome) in childhood and in adulthood were used as outcomes. Analyses were adjusted for age and sex. Results In childhood, participants without siblings had higher body mass index (18.2 kg/m(2), 95% CI 18.0-18.3) than those with 1 sibling (17.9 kg/m(2), 95% CI 17.8-18.0) or more than 1 sibling (17.8 kg/m(2), 95% CI 17.7-17.9). Childhood physical activity index was lower among participants without siblings (SD -0.08, 95% CI -0.16-0.00) compared with participants with 1 sibling (SD 0.06, 95%CI 0.01-0.11) or more than 1 sibling (SD -0.02, 95% CI -0.07-0.03). OR for adulthood hypertension was lower among participants with 1 sibling (OR 0.73, 95% CI 0.54-0.98) and more than 1 sibling (OR 0.71, 95% CI 0.52-0.97) compared with participants with no siblings. OR for obesity was lower among participants with 1 sibling (OR 0.72, 95% CI 0.54-0.95) and more than 1 sibling (OR 0.75, 95% CI 0.56-1.01) compared with those with no siblings. Conclusions Children without siblings had poorer cardiovascular risk factor levels in childhood and in adulthood. The number of siblings could help identify individuals at increased risk that might benefit from early intervention.
  • Jelenkovic, Aline; Silventoinen, Karri; Tynelius, Per; Myrskylä, Mikko; Rasmussen, Finn (2013)
  • Vojinovic, Dina; Kalaoja, Marita; Trompet, Stella; Fischer, Krista; Shipley, Martin J.; Li, Shuo; Havulinna, Aki S.; Perola, Markus; Salomaa, Veikko; Yang, Qiong; Sattar, Naveed; Jousilahti, Pekka; Amin, Najaf; Satizabal, Claudia L.; Taba, Nele; Sabayan, Behnam; Vasan, Ramachandran S.; Ikram, M. Arfan; Stott, David J.; Ala-Korpela, Mika; Jukema, J. Wouter; Seshadri, Sudha; Kettunen, Johannes; Kivimaki, Mika; Esko, Tonu; van Duijn, Cornelia M. (2021)
    Objective To conduct a comprehensive analysis of circulating metabolites and incident stroke in large prospective population-based settings. Methods We investigated the association of metabolites with risk of stroke in 7 prospective cohort studies including 1,791 incident stroke events among 38,797 participants in whom circulating metabolites were measured by nuclear magnetic resonance technology. The relationship between metabolites and stroke was assessed with Cox proportional hazards regression models. The analyses were performed considering all incident stroke events and ischemic and hemorrhagic events separately. Results The analyses revealed 10 significant metabolite associations. Amino acid histidine (hazard ratio [HR] per SD 0.90, 95% confidence interval [CI] 0.85, 0.94; p = 4.45 x 10-5), glycolysis-related metabolite pyruvate (HR per SD 1.09, 95% CI 1.04, 1.14; p = 7.45 x 10-4), acute-phase reaction marker glycoprotein acetyls (HR per SD 1.09, 95% CI 1.03, 1.15; p = 1.27 x 10-3), cholesterol in high-density lipoprotein (HDL) 2, and several other lipoprotein particles were associated with risk of stroke. When focused on incident ischemic stroke, a significant association was observed with phenylalanine (HR per SD 1.12, 95% CI 1.05, 1.19; p = 4.13 x 10-4) and total and free cholesterol in large HDL particles. Conclusions We found association of amino acids, glycolysis-related metabolites, acute-phase reaction markers, and several lipoprotein subfractions with the risk of stroke. These findings support the potential of metabolomics to provide new insights into the metabolic changes preceding stroke.
  • Seppala, Ilkka; Kleber, Marcus E.; Bevan, Steve; Lyytikainen, Leo-Pekka; Oksala, Niku; Hernesniemi, Jussi A.; Makela, Kari-Matti; Rothwell, Peter M.; Sudlow, Cathie; Dichgans, Martin; Mononen, Nina; Vlachopoulou, Efthymia; Sinisalo, Juha; Delgado, Graciela E.; Laaksonen, Reijo; Koskinen, Tuomas; Scharnagl, Hubert; Kahonen, Mika; Markus, Hugh S.; Maez, Winfried; Lehtimaki, Terho (2016)
    Asymmetric and symmetric dimethylarginines (ADMA and SDMA) impair nitric oxide bioavailability and have been implicated in the pathogenesis of atrial fibrillation (AF). Alanine-glyoxylate aminotransferase 2 (AGXT2) is the only enzyme capable of metabolizing both of the dimethylarginines. We hypothesized that two functional AGXT2 missense variants (rs37369, V140I; rs16899974, V498L) are associated with AF and its cardioembolic complications. Association analyses were conducted using 1,834 individulas with AF and 7,159 unaffected individuals from two coronary angiography cohorts and a cohort comprising patients undergoing clinical exercise testing. In coronary angiography patients without structural heart disease, the minor A allele of rs16899974 was associated with any AF (OR = 2.07, 95% CI 1.59-2.68), and with paroxysmal AF (OR = 1.98, 95% CI 1.44-2.74) and chronic AF (OR = 2.03, 95% CI 1.35-3.06) separately. We could not replicate the association with AF in the other two cohorts. However, the A allele of rs16899974 was nominally associated with ischemic stroke risk in the meta-analysis of WTCCC2 ischemic stroke cohorts (3,548 cases, 5,972 controls) and with earlier onset of first-ever ischemic stroke (360 cases) in the cohort of clinical exercise test patients. In conclusion, AGXT2 variations may be involved in the pathogenesis of AF and its age-related thromboembolic complications.
  • Nykänen, Tarja; Pihlainen, Kai; Kyröläinen, Heikki; Fogelholm, Mikael (2020)
    Objectives: This observational follow-up study investigated the associations of nutrition and body composition with cardiovascular disease (CVD) risk factors, including pro-inflammatory biomarkers, in soldiers during a 6-month deployment. Material and Methods: Thirty-five male soldiers were assessed at months 0, 3 and 6, and their parameters, i.e., M +/- SD, were as follows: age 30.0 +/- 8.7 years, height 179 +/- 6 cm, and BMI 24.2 +/- 2.5 kg/m(2). Three-day food diaries were used for monitoring macronutrient intake. Body composition was estimated using bioimpedance. Fasting blood samples for lipids and pro-inflammatory biomarkers were collected, and blood pressure measurements were performed. Results: Carbohydrate intake increased and protein intake decreased at month 3 (p = 0.034, p <0.001), while body composition remained stable. Systolic blood pressure increased at month 6, while other CVD risk factors remained within the reference values. Fat mass and body fat percentage were associated positively with total and low density lipoprotein (LDL) cholesterol concentrations at all measurement points. A negative association was found between the change in fiber intake vs. the change in total (r = -0.36, p = 0.033) and LDL cholesterol (R = -0.39, p = 0.019). Conclusions: Lower fiber intake and a greater amount of body fat were associated with high total and LDL cholesterol concentrations. Nevertheless, the measured CVD risk factors remained within the reference values, except for the higher systolic blood pressure. A regular screening of body composition and a higher consumption of fiber-rich foods may promote cardiometabolic health in soldiers.
  • Siltari, Aino; Korpela, R.; Vapaatalo, H. (2016)
    Bradykinin exerts its vascular actions via two types of receptors, the non-constitutively expressed bradykinin receptor type 1 (BR1) and the constitutive type 2 receptor (BR2). Bradykinin-induced vasorelaxation is age-dependent, a phenomenon related to the varying amounts of BR1 and BR2 in the vasculature. Isoleucine-proline-proline (Ile-Pro-Pro), a bioactive tripeptide, lowers elevated blood pressure and improves impaired endothelium-dependent vasorelaxation in hypertensive rats. It inhibits angiotensin converting enzyme 1 (ACE1). Other mechanisms of action have also been postulated. The aims of the study were to clarify the underlying mechanisms of the age-dependency of bradykinin-induced vasodilatation such as the roles of the two bradykinin receptors, themas-receptor and synergism with Ile-Pro-Pro. The vascular response studies were conducted using mesenteric artery and aorta rings from normotensive 6 wk. (young) and 22 wk. (old) Wistar rats. Cumulative dosing of acetylcholine, bradykinin and angiotensin(1-7) (Ang(1-7))were tested in phenylephrine-induced vasoconstriction with or without 10 min pre-incubation with antagonists against BR1-, BR2- or mas-receptors,Ang(1-7) or ACE1-inhibitors captopril and Ile-Pro-Pro. The bradykinin-induced vasorelaxation in vitro was age-dependent and it was improved by pre incubation with Ile-Pro-Pro, especially in old rats with endothelial dysfunction. The mas-receptor antagonist, D-Pro7-Ang(1-7) abolished bradykinin-induced relaxation totally. Interestingly, BR1 and BR2 antagonists only slightly reduced bradykinin-induced vasorelaxation, as an evidence for the involvement of other mechanisms in addition to receptor activation. In conclusion, bradykinin-induced vasorelaxation was age -dependent and He-Pro-Pro improved it. Mas receptor antagonist abolished relaxation while bradykinin receptor antagonist only slightly reduced it, suggesting that bradykinin-induced vasorelaxation is regulated also by other mechanisms than the classical BR1/BR2 pathway. (C) 2016 Elsevier Inc: All rights reserved.
  • Dauvilliers, Yves; Bogan, Richard K.; Sonka, Karel; Partinen, Markku; Foldvary-Schaefer, Nancy; Thorpy, Michael J. (2022)
    Lower-sodium oxybate (LXB) is an oxybate medication approved to treat cataplexy or excessive daytime sleepiness (EDS) in patients with narcolepsy 7 years of age and older in the United States. LXB was developed as an alternative to sodium oxybate (SXB), because the incidence of cardiovascular comorbidities is higher in patients with narcolepsy and there is an elevated cardiovascular risk associated with high sodium consumption. LXB has a unique formulation of calcium, magnesium, potassium, and sodium ions, containing 92% less sodium than SXB. Whereas the active oxybate moiety is the same for LXB and SXB, their pharmacokinetic profiles are not bioequivalent; therefore, a phase 3 trial in participants with narcolepsy was conducted for LXB. This review summarizes the background on oxybate as a therapeutic agent and its potential mechanism of action on the gammaaminobutyric acid type B (GABA B ) receptor at noradrenergic and dopaminergic neurons, as well as at thalamocortical neurons. The rationale leading to the development of LXB as a lower-sodium alternative to SXB and the key efficacy and safety data supporting its approval for both adult and pediatric patients with narcolepsy are also discussed. LXB was approved in August 2021 in the United States for the treatment of idiopathic hypersomnia in adults. Potential future developments in the field of oxybate medications may include novel formulations and expanded indications for other diseases.
  • Karvonen, Risto; Sipola, Marika; Kiviniemi, Antti; Tikanmäki, Marjaana; Järvelin, Marjo-Riitta; Eriksson, Johan G.; Tulppo, Mikko; Vääräsmäki, Marja; Kajantie, Eero (2019)
    Objective To evaluate cardiac autonomic function in adults born preterm. Study design We studied the association between prematurity and cardiac autonomic function using heart rate variability measurements in 600 adults (mean age of 23.3 years) from a geographically based cohort in Northern Finland. There were 117 young adults born early preterm (= 37 weeks, controls). Autonomic function was analyzed by calculating time and frequency domain heart rate variability measurements using linear regression. Results Compared with controls, the mean difference in root mean square of successive differences (indicating cardiac vagal activity) was -12.0% (95% CI -22.2%, -0.5%, adjusted for sex, age, source cohort, and season P = .04) for the early preterm group and -7.8% (-16.8%, 2.0%, P = .12) for the late preterm group. Mean differences with controls in low frequency power (indicating cardiac vagal activity, including some sympathetic- and baroreflex-mediated effects) were -13.6% (-26.7%, 1.8%, P = .08) for the early pretermgroup and -16.4% (-27.0%, -4.3%, P = .01) for the late preterm group. Mean differences in high frequency power (quantifying cardiac vagal modulation in respiratory frequency) were -19.2% (-36.6%, 2.9%, P = .09) for the early preterm group and -13.8% (-29.4%, 5.3%, P = .15) for the late preterm group. Differences were attenuated when controlled for body mass index and physical activity. Conclusions Our results suggest altered autonomic regulatory control in adults born preterm, including those born late preterm. Altered autonomic regulatory control may contribute to increased cardiovascular risk in adults born preterm.