Browsing by Subject "hypertension"

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  • Palmu, Joonatan; Salosensaari, Aaro; Havulinna, Aki S.; Cheng, Susan; Inouye, Michael; Jain, Mohit; Salido, Rodolfo A.; Sanders, Karenina; Brennan, Caitriona; Humphrey, Gregory C.; Sanders, Jon G.; Vartiainen, Erkki; Laatikainen, Tiina; Jousilahti, Pekka; Salomaa, Veikko; Knight, Rob; Lahti, Leo; Niiranen, Teemu J. (2020)
    Background Several small-scale animal studies have suggested that gut microbiota and blood pressure (BP) are linked. However, results from human studies remain scarce and conflicting. We wanted to elucidate the multivariable-adjusted association between gut metagenome and BP in a large, representative, well-phenotyped population sample. We performed a focused analysis to examine the previously reported inverse associations between sodium intake and Lactobacillus abundance and between Lactobacillus abundance and BP. Methods and Results We studied a population sample of 6953 Finns aged 25 to 74 years (mean age, 49.212.9 years; 54.9% women). The participants underwent a health examination, which included BP measurement, stool collection, and 24-hour urine sampling (N=829). Gut microbiota was analyzed using shallow shotgun metagenome sequencing. In age- and sex-adjusted models, the alpha (within-sample) and beta (between-sample) diversities of taxonomic composition were strongly related to BP indexes (P diversity was only associated with diastolic BP (P=0.032). However, we observed significant, mainly positive, associations between BP indexes and 45 microbial genera (P Conclusions Although the associations between overall gut taxonomic composition and BP are weak, individuals with hypertension demonstrate changes in several genera. We demonstrate strong negative associations of certain Lactobacillus species with sodium intake and BP, highlighting the need for experimental studies.
  • Shiri, Rahman; Heliovaara, Markku; Moilanen, Leena; Viikari, Jorma; Liira, Helena Johanna; Viikari-Juntura, Eira (2011)
  • Bonamy, Anna-Karin Edstedt; Mohlkert, Lilly-Ann; Hallberg, Jenny; Liuba, Petru; Fellman, Vineta; Domellof, Magnus; Norman, Mikael (2017)
    Background-Advances in perinatal medicine have increased infant survival after very preterm birth. Although this progress is welcome, there is increasing concern that preterm birth is an emerging risk factor for hypertension at young age, with implications for the lifetime risk of cardiovascular disease. Methods and Results-We measured casual blood pressures (BPs) in a population-based cohort of 6-year-old survivors of extremely preterm birth (<27 gestational weeks; n=171) and in age-and sex-matched controls born at term (n=172). Measured BP did not differ, but sex, age-, and height-adjusted median z scores were 0.14 SD higher (P=0.02) for systolic BP and 0.10 SD higher (P=0.01) for diastolic BP in children born extremely preterm than in controls. Among children born extremely preterm, shorter gestation, higher body mass index, and higher heart rate at follow-up were all independently associated with higher BP at 6 years of age, whereas preeclampsia, smoking in pregnancy, neonatal morbidity, and perinatal corticosteroid therapy were not. In multivariate regression analyses, systolic BP decreased by 0.10 SD (P=0.08) and diastolic BP by 0.09 SD (P=0.02) for each week-longer gestation. Conclusions-Six-year-old children born extremely preterm have normal but slightly higher BP than their peers born at term. Although this finding is reassuring for children born preterm and their families, follow-up at older age is warranted.
  • Einwaller, Joy; Painer, Johanna; Raekallio, Marja; Gasch, Kristina; Restitutti, Flavia; Auer, Ulrike; Stalder, Gabrielle L. (2020)
    Objective To determine the effect of intravenous vatinoxan administration on bradycardia, hypertension and level of anaesthesia induced by medetomidine-tiletamine-zolazepam in red deer (Cervus elaphus). Study design and animals A total of 10 healthy red deer were enrolled in a randomized, controlled, experimental, crossover study. Methods Deer were administered a combination of 0.1 mg kg-1 medetomidine hydrochloride and 2.5 mg kg-1 tiletamine-zolazepam intramuscularly, followed by 0.1 mg kg-1 vatinoxan hydrochloride or equivalent volume of saline intravenously (IV) 35 minutes after anaesthetic induction. Heart rate (HR), mean arterial blood pressure (MAP), respiration rate (fR), end-tidal CO2 (PE′CO2), arterial oxygen saturation (SpO2), rectal temperature (RT) and level of anaesthesia were assessed before saline/vatinoxan administration (baseline) and at intervals for 25 minutes thereafter. Differences within treatments (change from baseline) and between treatments were analysed with linear mixed effect models (p <0.05). Results Maximal (81 ± 10 beats minute-1) HR occurred 90 seconds after vatinoxan injection and remained significantly above baseline (42 ± 4 beats minute-1) for 15 minutes. MAP significantly decreased from baseline (122 ± 10 mmHg) to a minimum MAP of 83 ± 6 mmHg 60 seconds after vatinoxan and remained below baseline until end of anaesthesia. HR remained unchanged from baseline (43 ± 5 beats minute-1) with the saline treatment, while MAP decreased significantly (112 ± 16 mmHg) from baseline after 20 minutes. PE′CO2, fR, and SpO2 showed no significant differences between treatments, while RT decreased significantly 25 minutes after vatinoxan. Level of anaesthesia was not significantly influenced by vatinoxan. Conclusion and clinical relevance Vatinoxan reversed hypertension and bradycardia induced by medetomidine without causing hypotension or affecting the level of anaesthesia in red deer. However, the effect on HR subsided 15 minutes after vatinoxan IV administration. Vatinoxan has the potential to reduce anaesthetic side effects in non-domestic ruminants immobilized with medetomidine-tiletamine-zolazepam.
  • Fernandez, Celine; Rysä, Jaana; Ström, Kristoffer; Nilsson, Jan; Engström, Gunnar; Orho-Melander, Marju; Ruskoaho, Heikki; Melander, Olle (2020)
    Aims Hypertension is the leading cause for the development of heart failure (HF). Here, we aimed to identify cardiomyocyte stretch-induced circulating biomarkers for predicting hypertension-associated HF. Methods and results Circulating levels of 149 proteins were measured by proximity extension assay at baseline examination in 4742 individuals from the Malmo Diet and Cancer study. Protein levels were compared with stretch-activated gene expression changes in cultured neonatal rat ventricular myocytes (NRVMs) in response to 1-48 h of mechanical stretch. We also studied the association between protein levels and hypertension and HF incidence using respectively binary logistic and Cox regressions. Levels of 35 proteins were differentially expressed after Bonferroni correction in incident HF vs. control (P <3.4E-4). Growth differentiation factor-15 (GDF-15), interleukin-6 (IL-6), IL-1 receptor type 1, and urokinase plasminogen activator surface receptor had corresponding mRNA levels up-regulated by stretch in NRVMs at all time points (P <0.05). These four proteins were individually associated with increased risk of HF after age and sex adjustment [hazard ratio (HR) per standard deviation: 1.19 Conclusions Cardiomyocyte mRNA levels of GDF-15 and IL-6 are consistently up-regulated by stretch, and their circulating protein levels predict HF in hypertensive subjects independently of NT-proBNP during long-term follow-up. Our results encourage further studies on lower blood pressure goals in hypertensive subjects with high GDF-15 and IL-6, and interventions targeted at stretch-induced cardiomyocyte expressed biomarkers.
  • Palmu, Joonatan; Tikkanen, Emmi; Havulinna, Aki S.; Vartiainen, Erkki; Lundqvist, Annamari; Ruuskanen, Matti O.; Perola, Markus; Ala-Korpela, Mika; Jousilahti, Pekka; Wurtz, Peter; Salomaa, Veikko; Lahti, Leo; Niiranen, Teemu (2022)
    Objective: Previous studies on the association between metabolic biomarkers and hypertension have been limited by small sample sizes, low number of studied biomarkers, and cross-sectional study design. In the largest study to date, we assess the cross-sectional and longitudinal associations between high-abundance serum biomarkers and blood pressure (BP). Methods: We studied cross-sectional (N = 36 985; age 50.5 +/- 14.2; 53.1% women) and longitudinal (N = 4197; age 49.4 +/- 11.8, 55.3% women) population samples of Finnish individuals. We included 53 serum biomarkers and other detailed lipoprotein subclass measures in our analyses. We studied the associations between serum biomarkers and BP using both conventional statistical methods and a machine learning algorithm (gradient boosting) while adjusting for clinical risk factors. Results: Fifty-one of 53 serum biomarkers were cross-sectionally related to BP (adjusted P < 0.05 for all). Conventional linear regression modeling demonstrated that LDL cholesterol, remnant cholesterol, apolipoprotein B, and acetate were positively, and HDL particle size was negatively, associated with SBP change over time (adjusted P < 0.05 for all). Adding serum biomarkers (cross-sectional root-mean-square error: 16.27 mmHg; longitudinal: 17.61 mmHg) in the model with clinical measures (cross-sectional: 16.70 mmHg; longitudinal 18.52 mmHg) improved the machine learning model fit. Glucose, albumin, triglycerides in LDL, glycerol, VLDL particle size, and acetoacetate had the highest importance scores in models related to current or future BP. Conclusion: Our results suggest that serum lipids, and particularly LDL-derived and VLDL-derived cholesterol measures, and glucose metabolism abnormalities are associated with hypertension onset. Use of serum metabolite determination could improve identification of individuals at high risk of developing hypertension.
  • Zhou, Bin; Bentham, James; Di Cesare, Mariachiara; Bixby, Honor; Danaei, Goodarz; Hajifathalian, Kaveh; Taddei, Cristina; Carrillo-Larco, Rodrigo M.; Djalalinia, Shirin; Khatibzadeh, Shahab; Lugero, Charles; Peykari, Niloofar; Zhang, Wan Zhu; Bennett, James; Bilano, Ver; Stevens, Gretchen A.; Cowan, Melanie J.; Riley, Leanne M.; Chen, Zhengming; Hambleton, Ian R.; Jackson, Rod T.; Kengne, Andre Pascal; Khang, Young-Ho; Laxmaiah, Avula; Liu, Jing; Malekzadeh, Reza; Neuhauser, Hannelore K.; Soric, Maroje; Starc, Gregor; Sundstrom, Johan; Woodward, Mark; Ezzati, Majid; Abarca-Gomez, Leandra; Abdeen, Ziad A.; Abu-Rmeileh, Niveen M.; Acosta-Cazares, Benjamin; Adams, Robert J.; Aekplakorn, Wichai; Afsana, Kaosar; Aguilar-Salinas, Carlos A.; Agyemang, Charles; Ahmad, Noor Ani; Ahmadvand, Alireza; Ahrens, Wolfgang; Ajlouni, Kamel; Akhtaeva, Nazgul; Eriksson, Johan G.; Kajantie, Eero O.; Kauhanen, Jussi; Peltonen, Markku; Salonen, Jukka Tapio; Saramies, Jouko L. (2018)
    Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probit-transformed) prevalence of raised blood pressure and age-group-and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the high-income Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups.
  • Louca, Panayiotis; Nogal, Ana; Moskal, Aurelie; Goulding, Neil J.; Shipley, Martin J.; Alkis, Taryn; Lindbohm, Joni; Hu, Jie; Kifer, Domagoj; Wang, Ni; Chawes, Bo; Rexrode, Kathryn M.; Ben-Shlomo, Yoav; Kivimaki, Mika; Murphy, Rachel A.; Yu, Bing; Gunter, Marc J.; Suhre, Karsten; Lawlor, Deborah A.; Mangino, Massimo; Menni, Cristina (2022)
    Hypertension is the main modifiable risk factor for cardiovascular morbidity and mortality but discovering molecular mechanisms for targeted treatment has been challenging. Here we investigate associations of blood metabolite markers with hypertension by integrating data from nine intercontinental cohorts from the COnsortium of METabolomics Studies. We included 44,306 individuals with circulating metabolites (up to 813). Metabolites were aligned and inverse normalised to allow intra-platform comparison. Logistic models adjusting for covariates were performed in each cohort and results were combined using random-effect inverse-variance meta-analyses adjusting for multiple testing. We further conducted canonical pathway analysis to investigate the pathways underlying the hypertension-associated metabolites. In 12,479 hypertensive cases and 31,827 controls without renal impairment, we identified 38 metabolites, associated with hypertension after adjusting for age, sex, body mass index, ethnicity, and multiple testing. Of these, 32 metabolite associations, predominantly lipid (steroids and fatty acyls) and organic acids (amino-, hydroxy-, and keto-acids) remained after further adjusting for comorbidities and dietary intake. Among the identified metabolites, 5 were novel, including 2 bile acids, 2 glycerophospholipids, and ketoleucine. Pathway analysis further implicates the role of the amino-acids, serine/glycine, and bile acids in hypertension regulation. In the largest cross-sectional hypertension-metabolomics study to date, we identify 32 circulating metabolites (of which 5 novel and 27 confirmed) that are potentially actionable targets for intervention. Further in-vivo studies are needed to identify their specific role in the aetiology or progression of hypertension.
  • Helanterä, Ilkka; Ibrahim, Hassan N.; Lempinen, Marko; Finne, Patrik (2020)
    Background and objectives Increased donor age is one of the most important risk factors for delayed graft function (DGF), and previous studies suggest that the harmful effect of cold ischemia time is increased in kidneys from older donors. Our aim was to study the association of increased donor age and cold ischemia time with the risk of delayed graft function in a large cohort kidney transplants from the current era. Design, setting, participants, & measurements The Scientific Registry of Transplant Recipients was used for this observational, retrospective registry analysis to identify all deceased donor kidney transplantations in the United States between 2010 and September 2018, who were on dialysis pretransplantation (n=90,810). The association of donor age and cold ischemia time with the risk of DGF was analyzed in multivariable models adjusted for recipient characteristics (age, race, sex, diabetes, calculated panel-reactive antibodies, pretransplant dialysis duration) and donor characteristics (cause of death, sex, race, body mass index, creatinine, donation after circulatory death status, history of hypertension, and HLA mismatch). Results Cold ischemia time and donor age were independently associated with the risk of DGF, but the risk of DGF was not statistically significantly lower in donor age categories between 50 and 64 years, compared with donors ?65 years. The harmful association of cold ischemia time was not higher in kidneys from older donors in any age category, not even among donation after circulatory death donors. When donor risk was assessed with kidney donor profile index, although a statistically significant interaction with cold ischemia time was found, no practically meaningful increase in cold-ischemia susceptibility of kidneys with a high kidney donor profile index was found. Conclusions We were unable to demonstrate an association between donor age and DGF. The association of longer cold ischemia time with the risk of DGF was not magnified in older or more marginal donors.
  • Johnson, Linda S. B.; Salonen, Minna; Kajantie, Eero; Conen, David; Healey, Jeff S.; Osmond, Clive; Eriksson, Johan G. (2017)
    Background-Early life risk factors are associated with cardiometabolic disease, but have not been fully studied in atrial fibrillation (AF). There are discordant results from existing studies of birth weight and AF, and the impact of maternal body size, gestational age, placental size, and birth length is unknown. Methods and Results-The Helsinki Birth Cohort Study includes 13 345 people born as singletons in Helsinki in the years 1934-1944. Follow-up was through national registries, and ended on December 31, 2013, with 907 incident cases. Cox regression analyses stratified on year of birth were constructed for perinatal variables and incident AF, adjusting for offspring sex, gestational age, and socioeconomic status at birth. There was a significant U-shaped association between birth weight and AF (P for quadratic term = 0.01). The lowest risk of AF was found among those with a birth weight of 3.4 kg (3.8 kg for women [85th percentile] and 3.0 kg for men [17th percentile]). High maternal body mass index (>= 30 kg/m(2)) predicted offspring AF; hazard ratio 1.36 (95% CI 1.07-1.74, P = 0.01) compared with normal body mass index ( Conclusions-High maternal body mass index during pregnancy and maternal height are previously undescribed predictors of offspring AF. Efforts to prevent maternal obesity might reduce later AF in offspring. Birth weight has a U-shaped relation to incident AF independent of other perinatal variables.
  • Al-Raddadi, Rajaa; Al-Ahmadi, Jawaher; Bahijri, Suhad; Jambi, Hanan; Enani, Sumia; Eldakhakhny, Basmah Medhat; Alsheikh, Lubna; Borai, Anwar; Tuomilehto, Jaakko (2021)
    The association between lifestyle practices, obesity and increased BP are under-investigated. We aimed to investigate this association to identify the factors associated with hypertension and prehypertension in Saudis. Non-diabetic adults were recruited from public healthcare centers using a cross-sectional design. Recruits were interviewed using a predesigned questionnaire. Weight, height, waist circumference (WC), hip circumference (HC), neck circumference (NC) and BP were measured. The variables were analyzed by comparing the prehypertensive and hypertensive groups with the normotensive group. A total of 1334 adults were included. The study found that 47.2% of men and 24.7% of women were prehypertensive, and 15.1% of men and 14.4% of women were hypertensive. High BMI, WC, NC, and WC: HC ratios were associated with an increased risk of prehypertension and hypertension in men and women. Low physical activity was associated with an increased risk of elevated BP in men, while sleep duration of & LE;6 h and sitting for & GE;4 h were associated with increased risk in women. Women from central Asia, southeast Asia, and those of mixed origin had a higher prevalence of hypertension compared to those from Arabian tribes. In conclusion, prehypertension and hypertension increase with age and obesity. Gender differences were apparent in the association between several lifestyle practices and prehypertension or hypertension among various ethnic/racial groups.
  • Salo, Perttu P.; Havulinna, Aki S.; Tukiainen, Taru; Raitakari, Olli; Lehtimäki, Terho; Kähönen, Mika; Kettunen, Johannes; Männikkö, Minna; Eriksson, Johan G.; Jula, Antti; Blankenberg, Stefan; Zeller, Tanja; Salomaa, Veikko; Kristiansson, Kati; Perola, Markus (2017)
    Background Cardiomyocytes secrete atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in response to mechanical stretching, making them useful clinical biomarkers of cardiac stress. Both human and animal studies indicate a role for ANP as a regulator of blood pressure with conflicting results for BNP. Methods and Results We used genome-wide association analysis (n=6296) to study the effects of genetic variants on circulating natriuretic peptide concentrations and compared the impact of natriuretic peptide-associated genetic variants on blood pressure (n=27059). Eight independent genetic variants in 2 known (NPPA-NPPB and POC1B-GALNT4) and 1 novel locus (PPP3CC) associated with midregional proANP (MR-proANP), BNP, aminoterminal proBNP (NT-proBNP), or BNP:NT-proBNP ratio. The NPPA-NPPB locus containing the adjacent genes encoding ANP and BNP harbored 4 independent cis variants with effects specific to either midregional proANP or BNP and a rare missense single nucleotide polymorphism in NT-proBNP seriously altering its measurement. Variants near the calcineurin catalytic subunit gamma gene PPP3CC and the polypeptide N-acetylgalactosaminyltransferase 4 gene GALNT4 associated with BNP:NT-proBNP ratio but not with BNP or midregional proANP, suggesting effects on the post-translational regulation of proBNP. Out of the 8 individual variants, only those correlated with midregional proANP had a statistically significant albeit weak impact on blood pressure. The combined effect of these 3 single nucleotide polymorphisms also associated with hypertension risk (P=8.2x10(-4)). Conclusions Common genetic differences affecting the circulating concentration of ANP associated with blood pressure, whereas those affecting BNP did not, highlighting the blood pressure-lowering effect of ANP in the general population.
  • Singh, Sonal; Warren, Helen R.; Hiltunen, Timo P.; McDonough, Caitrin W.; El Rouby, Nihal; Salvi, Erika; Wang, Zhiying; Garofalidou, Tatiana; Fyhrquist, Frej; Kontula, Kimmo K.; Glorioso, Valeria; Zaninello, Roberta; Glorioso, Nicola; Pepine, Carl J.; Munroe, Patricia B.; Turner, Stephan T.; Chapman, Arlene B.; Boerwinkle, Eric; Johnson, Julie A.; Gong, Yan; Cooper-DeHoff, Rhonda M. (2019)
    Background-There exists a wide interindividual variability in blood pressure (BP) response to beta(1)-blockers. To identify the genetic determinants of this variability, we performed a pharmacogenomic genome-wide meta-analysis of genetic variants beta(1)-influencing blocker BP response. Methods and Results-Genome-wide association analysis for systolic BP and diastolic BP response to beta(1)-blockers from 5 randomized clinical trials consisting of 1254 patients with hypertension of European ancestry were combined in meta-analysis and single nucleotide polymorphisms (SNPs) with P Conclusions-Data from randomized clinical trials of 8 European ancestry and 2 black cohorts support the assumption that BST1 containing locus on chromosome 4 is associated with beta(1)-blocker BP response. Given the previous associations of this region with BP, this is a strong candidate region for future functional studies and potential use in precision medicine approaches for BP management and risk prediction.
  • Kajantie, Eero; Osmond, Clive; Eriksson, Johan G. (2017)
    BACKGROUND: Women with hypertensive disorders in pregnancy are at an increased risk of cardiovascular disease and type 2 diabetes later in life. Offspring born from these hypertensive pregnancies have increased levels of cardiovascular risk factors; whether they are at an increased risk of type 2 diabetes is not known. OBJECTIVE: The objective of the investigation was to study the risk of type 2 diabetes in the adult offspring exposed to maternal preeclampsia or gestational hypertension in utero. STUDY DESIGN: We studied 5335 members of the Helsinki Birth Cohort Study, who were born between 1934 and 1944 and who lived in Finland in 1995 when the National Medication Purchase Register was initiated. We ascertained gestational hypertension and preeclampsia according to modern criteria by using maternal and birth records. We defined type 2 diabetes through purchases of antidiabetic medication recorded in the comprehensive National Medication Purchase Register, excluding the 31 subjects who had purchased only insulin. We used Cox regression to assess hazard ratios for type 2 diabetes. RESULTS: A total of 590 men (21.6%) and 433 women (16.9%) had purchased medication for diabetes. The hazard ratio for type 2 diabetes for offspring exposed to any maternal hypertension in pregnancy was 1.13 (95% confidence interval, 1.00-1.29; n = 1780). For maternal gestational hypertension, it was 1.15 (95% confidence interval, 1.00-1.33; n = 1336) and for preeclampsia 0.98 (95% confidence interval, 0.71-1.34; n = 231). For type 2 diabetes with first medication purchase before 62 years, the corresponding hazard ratios were 1.25 (95% confidence interval, 1.04-1.51); 1.28 (95% confidence interval, 1.05-1.58), and 1.18 (95% confidence interval, 0.75-1.84). The hazard ratios were similar when adjusted for birthweight SD score for gestation, length of gestation, maternal body mass index in late pregnancy, height, age, and parity and for childhood or adult socioeconomic position. An increased risk of type 2 diabetes was also associated with low birthweight SD score, independent of the association with gestational hypertension. CONCLUSION: Offspring exposed to maternal gestational hypertension in utero have an increased risk of type 2 diabetes in late adult life. This finding underlines the role of the whole spectrum of hypertensive disorders of pregnancy as risk factors of offspring disease throughout life. It also reinforces previous suggestions that adult health care providers should incorporate birth histories when evaluating an individual's risk to develop type 2 diabetes.
  • 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.
  • Benetos, Athanase; Petrovic, Mirko; Strandberg, Timo (2019)
    The prevalence of arterial hypertension, particularly systolic hypertension, is constantly rising worldwide. This is mainly the clinical expression of arterial stiffening as a result of the population's aging. Chronic elevation in blood pressure represents a major risk factor not only for cardiovascular morbidity and mortality but also for cognitive decline and loss of autonomy later in life. Clinical evidence obtained in community-dwelling older people with few comorbidities and preserved autonomy supports the beneficial effects of lowering blood pressure in older hypertensive subjects even after the age of 80 years. However, observational studies in frail older individuals treated for hypertension have shown higher morbidity and mortality rates compared with those with lower blood pressure levels. Clearly, in very old subjects, the therapeutic strategy of one size fits all cannot be applied because of the enormous functional heterogeneity in these individuals. Geriatric medicine proposes taking into account the function/ frailty/ autonomy status of older people. In the present review, we propose to adapt the antihypertensive treatment using an easy-to-apply visual numeric scale allowing the identification of 3 different patient profiles according to the functional status and autonomy for activities of daily living. For the preserved function profile, strategies should be those proposed for younger old adults. For the loss of function/ preserved activities of daily living' profile, a more detailed geriatric assessment is needed to define the benefit/ risk balance as well as requirements for the tailoring of the various therapeutic strategies. Lastly, for the loss of function and altered activities of daily living' profile, therapeutic strategies should be thoroughly reassessed, including deprescribing (when considered appropriate). In the near future, controlled trials are necessary for the most frail older subjects (ie, in those systematically excluded from previous clinical trials) to gain stronger evidence regarding the benefits of the various therapeutic strategies.
  • Kazmi, Nabila; Sharp, Gemma C.; Reese, Sarah E.; Vehmeijer, Florianne O.; Lahti, Jari; Page, Christian M.; Zhang, Weiming; Rifas-Shiman, Sheryl L.; Rezwan, Faisal I.; Simpkin, Andrew J.; Burrows, Kimberley; Richardson, Tom G.; Ferreira, Diana L. Santos; Fraser, Abigail; Harmon, Quaker E.; Zhao, Shanshan; Jaddoe, Vincent W. V.; Czamara, Darina; Binder, Elisabeth B.; Magnus, Maria C.; Haberg, Siri E.; Nystad, Wenche; Nohr, Ellen A.; Starling, Anne P.; Kechris, Katerina J.; Yang, Ivana V.; DeMeo, Dawn L.; Litonjua, Augusto A.; Baccarelli, Andrea; Oken, Emily; Holloway, John W.; Karmaus, Wilfried; Arshad, Syed H.; Dabelea, Dana; Sorensen, Thorkild I. A.; Laivuori, Hannele; Räikkönen, Katri; Felix, Janine F.; London, Stephanie J.; Hivert, Marie-France; Gaunt, Tom R.; Lawlor, Debbie A.; Relton, Caroline L. (2019)
    Hypertensive disorders of pregnancy (HDP) are associated with low birth weight, shorter gestational age, and increased risk of maternal and offspring cardiovascular diseases later in life. The mechanisms involved are poorly understood, but epigenetic regulation of gene expression may play a part. We performed meta-analyses in the Pregnancy and Childhood Epigenetics Consortium to test the association between either maternal HDP (10 cohorts; n=5242 [cases=476]) or preeclampsia (3 cohorts; n=2219 [cases=135]) and epigenome-wide DNA methylation in cord blood using the Illumina HumanMethylation450 BeadChip. In models adjusted for confounders, and with Bonferroni correction, HDP and preeclampsia were associated with DNA methylation at 43 and 26 CpG sites, respectively. HDP was associated with higher methylation at 27 (63%) of the 43 sites, and across all 43 sites, the mean absolute difference in methylation was between 0.6% and 2.6%. Epigenome-wide associations of HDP with offspring DNA methylation were modestly consistent with the equivalent epigenome-wide associations of preeclampsia with offspring DNA methylation (R-2=0.26). In longitudinal analyses conducted in 1 study (n=108 HDP cases; 550 controls), there were similar changes in DNA methylation in offspring of those with and without HDP up to adolescence. Pathway analysis suggested that genes located at/near HDP-associated sites may be involved in developmental, embryogenesis, or neurological pathways. HDP is associated with offspring DNA methylation with potential relevance to development.
  • Huang, Yisong; Ollikainen, Miina; Muniandy, Maheswary; Zhang, Tao; van Dongen, Jenny; Hao, Guang; van Der Most, Peter J.; Pan, Yue; Pervjakova, Natalia; Sun, Yan; Hui, Qin; Lahti, Jari; Fraszczyk, Eliza; Lu, Xueling; Sun, Dianjianyi; Richard, Melissa A.; Willemsen, Gonneke; Heikkila, Kauko; Leach, Irene Mateo; Mononen, Nina; Kähönen, Mika; Hurme, Mikko A.; Raitakari, Olli T.; Drake, Amanda J.; Perola, Markus; Nuotio, Marja-Liisa; Huang, Yunfeng; Khulan, Batbayar; Räikkönen, Katri; Wolffenbuttel, Bruce H. R.; Zhernakova, Alexandra; Fu, Jingyuan; Zhu, Haidong; Dong, Yanbin; van Vliet-Ostaptchouk, Jana V.; Franke, Lude; Eriksson, Johan G.; Fornage, Myriam; Milani, Lili; Lehtimäki, Terho; Vaccarino, Viola; Boomsma, Dorret; van Der Harst, Pim; de Geus, Eco J. C.; Salomaa, Veikko; Li, Shengxu; Chen, Wei; Su, Shaoyong; Wilson, James; Snieder, Harold; Kaprio, Jaakko; Wang, Xiaoling (2020)
    We conducted an epigenome-wide association study meta-analysis on blood pressure (BP) in 4820 individuals of European and African ancestry aged 14 to 69. Genome-wide DNA methylation data from peripheral leukocytes were obtained using the Infinium Human Methylation 450k BeadChip. The epigenome-wide association study meta-analysis identified 39 BP-related CpG sites withP
  • Kivelä, Jemina; Sormunen-Harju, Heidi; Girchenko, Polina; Huvinen, Emilia; Stach-Lempinen, Beata; Kajantie, Eero; Villa, Pia M.; Reynolds, Rebecca M.; Hämäläinen, Esa K.; Lahti-Pulkkinen, Marius; Murtoniemi, Katja K.; Laivuori, Hannele; Eriksson, Johan G.; Räikkönen, Katri; Koivusalo, Saila B. (2021)
    Context: Comprehensive assessment of metabolism in maternal obesity and pregnancy disorders can provide information about the shared maternal-fetal milieu and give insight into both maternal long-term health and intergenerational transmission of disease burden. Objective: To assess levels, profiles, and change in the levels of metabolic measures during pregnancies complicated by obesity, gestational diabetes (GDM), or hypertensive disorders. Design, Setting and Participants: A secondary analysis of 2 study cohorts, PREDO and RADIEL, including 741 pregnant women. Main Outcome Measures: We assessed 225 metabolic measures by nuclear magnetic resonance in blood samples collected at median 13 [interquartile range (IQR) 12.4-13.7], 20 (IQR 19.3-23.0), and 28 (27.0-35.0) weeks of gestation. Results: Across all 3 time points women with obesity [body mass index (BMI) >= 30 kg/m(2)] in comparison to normal weight (BMI 18.5-24.99 kg/m(2)) had significantly higher levels of most very-low-density lipoprotein-related measures, many fatty and most amino acids, and more adverse metabolic profiles. The change in the levels of most metabolic measures during pregnancy was smaller in obese than in normal weight women. GDM, preeclampsia, and chronic hypertension were associated with metabolic alterations similar to obesity. The associations of obesity held after adjustment for GDM and hypertensive disorders, but many of the associations with GDM and hypertensive disorders were rendered nonsignificant after adjustment for BMI and the other pregnancy disorders. Conclusions: This study shows that the pregnancy-related metabolic change is smaller in women with obesity, who display metabolic perturbations already in early pregnancy. Metabolic alterations of obesity and pregnancy disorders resembled each other suggesting a shared metabolic origin.
  • Vihlman, Outi (Helsingin yliopisto, 2019)
    Objective Depression and high blood pressure are becoming more common problems, but their relation remains unclear. This master's thesis studied the relation between depression and high blood pressure in the longitudinal Young Finns Study over a follow-up of four years. The aim was to examine whether 1) baseline depressive symptoms predict blood pressure over the follow-up, 2) the relation between depression and blood pressure differs among men and women, 3) health choices affect the relation, and 4) there is a relation between the duration of depression and blood pressure. Methods The participants (N=909) were about 42 years old, and 61 % of them were women. Their blood pressure and BDI-II depression scores were measured in 2007 ja 2011. Three-step regression analysis was used to predict the systolic and diastolic blood pressure based on the baseline depression score. The first model was controlled for age, gender and baseline blood pressure, the second model also for education and income, and the third model additionally for health choices. The average blood pressures of non-depressed, once depressed and twice depressed participants were compared in analysis of variance. The group comparisons were additionally controlled for age, gender and baseline blood pressure in analysis of covariance. Results and conclusions Baseline depressive symptoms did not predict blood pressure. Among women, a positive relation between depression and blood pressure was found in the first model, but not in the more controlled models. The relation between depression and blood pressure was partly explained by health choices; higher body mass index predicted higher blood pressure. Controlling for age, gender and baseline blood pressure, the duration of depression was connected to higher blood pressure; the diastolic blood pressure was higher, when the participant was depressed both in the beginning and end of the follow-up.