Browsing by Subject "STROKE"

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  • Lindbohm, Joni; Korja, Miikka; Jousilahti, Pekka; Salomaa, Veikko; Kaprio, Jaakko (2018)
    Background and aims: Studies report that both high and low total cholesterol (TC) elevates SAH risk. There are few prospective studies on high-density lipoproteins (HDL-C) and low-density lipoproteins (LDL-C), and apparently none concerns apolipoproteins A and B. We aimed to clarify the association between lipid profile and SAH risk. Methods: The National FINRISK study provided risk-factor data recorded at enrolment between 1972 and 2007. During 1.52 million person-years of follow-up until 2014, 543 individuals suffered from incident hospitalized SAH or outside-hospital-fatal SAH. Cox proportional hazards model was used to calculate the hazard ratios and multiple imputation predicted ApoA1, ApoB, and LDL-C values for cohorts from a time before apolipoprotein-measurement methods were available. Results: One SD elevation (1.28 mmol/l) in TC elevated SAH risk in men (hazard ratio (HR) 1.15 (95% CIs 1.00-1.32)). Low HDL-C levels increased SAH risk, as each SD decrease (0.37 mmol/l) in HDL-C raised the risk in women (HR 1.29 (95% CIs 1.07-1.55)) and men (HR 1.20 (95% CIs 1.14-1.27)). Each SD increase (0.29 g/l) in ApoA1 decreased SAH risk in women (HR 0.85 (95% CIs 0.74-0.97)) and men (HR 0.88 (95% CIs 0.76-1.02)). LDL-C (SD 1.07 mmol/l) and ApoB (SD 0.28 g/l) elevated SAH risk in men with HR 1.15 (95% CIs 1.01-1.31) and HR 1.26 (95% CIs 1.10-1.44) per one SD increase. Age did not change these findings. Conclusions: An adverse lipid profile seems to elevate SAH risk similar to its effect in other cardiovascular diseases, especially in men. Whether SAH incidence diminishes with increasing statin use remains to be studied. (C) 2018 Elsevier B.V. All rights reserved.
  • Andersen, Lise Geisler; Angquist, Lars; Eriksson, Johan G.; Forsen, Tom; Gamborg, Michael; Osmond, Clive; Baker, Jennifer L.; Sorensen, Thorkild I. A. (2010)
  • Liang, Yajun; Ngandu, Tiia; Laatikainen, Tiina; Soininen, Hilkka; Tuomilehto, Jaakko; Kivipelto, Miia; Qiu, Chengxuan (2020)
    Background Very few studies have explored the patterns of cardiovascular health (CVH) metrics in midlife and late life in relation to risk of dementia. We examined the associations of composite CVH metrics from midlife to late life with risk of incident dementia. Methods and findings This cohort study included 1,449 participants from the Finnish Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study, who were followed from midlife (baseline from1972 to 1987; mean age 50.4 years; 62.1% female) to late life (1998), and then 744 dementia-free survivors were followed further into late life (2005 to 2008). We defined and scored global CVH metrics based on 6 of the 7 components (i.e., smoking, physical activity, and body mass index [BMI] as behavioral CVH metrics; fasting plasma glucose, total cholesterol, and blood pressure as biological CVH metrics) following the modified American Heart Association (AHA)'s recommendations. Then, the composite global, behavioral, and biological CVH metrics were categorized into poor, intermediate, and ideal levels. Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. Data were analyzed with Cox proportional hazards and the Fine and Gray competing risk regression models. During the follow-up examinations, dementia was diagnosed in 61 persons in 1998 and additional 47 persons in 2005 to 2008. The fully adjusted hazard ratio (HR) of dementia was 0.71 (95% confidence interval [CI]: 0.43, 1.16; p = 0.174) and 0.52 (0.29, 0.93; p = 0.027) for midlife intermediate and ideal levels (versus poor level) of global CVH metrics, respectively; the corresponding figures for late-life global CVH metrics were 0.60 (0.22, 1.69; p = 0.338) and 0.91 (0.34, 2.41; p = 0.850). Compared with poor global CVH metrics in both midlife and late life, the fully adjusted HR of dementia was 0.25 (95% CI: 0.08, 0.86; p = 0.028) for people with intermediate global CVH metrics in both midlife and late life and 0.14 (0.02, 0.76; p = 0.024) for those with midlife ideal and late-life intermediate global CVH metrics. Having an intermediate or ideal level of behavioral CVH in both midlife and late life (versus poor level in both midlife and late life) was significantly associated with a lower dementia risk (HR range: 0.03 to 0.26; p <0.05), whereas people with midlife intermediate and late-life ideal biological CVH metrics had a significantly increased risk of dementia (p = 0.031). Major limitations of this study include the lack of data on diet and midlife plasma glucose, high rate of attrition, as well as the limited power for certain subgroup analyses. Conclusions In this study, we observed that having the ideal CVH metrics, and ideal behavioral CVH metrics in particular, from midlife onwards is associated with a reduced risk of dementia as compared with people having poor CVH metrics. Maintaining life-long health behaviors may be crucial to reduce late-life risk of dementia. Author summary Why was this study done? Dementia is a global public health problem, but there is currently no cure or a disease-modifying therapy for dementia. Simulation studies suggested that interventions targeting modifiable risk factors (e.g., cardiovascular factors) could prevent up to one-third of dementia cases. A better understanding of the life-long cardiovascular health (CVH) metrics and risk of dementia may facilitate the development of optimal intervention strategies. What did the researchers do and find? We examined the associations of CVH metrics in midlife and late life with risk of incident dementia in a population-based cohort of 1,449 participants in Finland followed for around 30 years. Compared with poor CVH metrics, the ideal global and behavioral CVH metrics in midlife were associated with a reduced risk of dementia, whereas the ideal biological CVH metrics in late life appeared to be associated with an increased risk of dementia. Having an intermediate or ideal level of behavioral CVH metrics from midlife onwards was associated with a late-life reduced risk of dementia. What do these findings mean? The association of ideal global CVH metrics with a reduced dementia risk disappeared from midlife to old age, driven largely by the age-varying association between biological CVH metrics and risk of dementia. Maintaining a life-long optimal level of CVH metrics, especially behavioral health metrics, may reduce late-life risk of dementia. The association of late-life ideal biological CVH metrics with an increased risk of dementia may largely reflect the potential of reverse causality.
  • Paju, Susanna; Pietiäinen, Milla; Liljestrand, John; Lahdentausta, Laura; Salminen, Aino; Kallio, Elisa; Mäntylä, Päivi; Buhlin, Kåre; Hörkkö, Sohvi; Sinisalo, Juha; Pussinen, Pirkko (2021)
    Aim To study the prevalence of carotid artery calcification (CAC) in relation to apical and marginal periodontitis, subgingival dysbiotic bacterial species and serum and saliva immune responses against them. In addition, the aim was to analyse the association of CAC with angiographically verified coronary artery disease (CAD) and mortality. Methodology In the present random Parogene cohort, the patients had an indication for coronary angiography. Apical and marginal periodontitis were diagnosed during clinical and radiographic oral examinations, and CAC on panoramic radiographs (n = 492). Presence and severity of CAD were registered from angiography. Subgingival dysbiotic bacterial species were quantitated using checkerboard DNA-DNA-hybridization, and serum and saliva antibody levels were determined by immunoassays. The cohort was followed-up for 10 years or until death (median 9.9, range 0.21-10.4) via linkage to the national death register. The statistical models were adjusted for age, gender, smoking, hypertension, diabetes and dyslipidemia. Results A total of 102 (20.7%) patients had detectable CAC, which was moderate in 81 (16.4%) and severe in 21 (4.3%). CAC was associated (OR, 95% CI) with severe apical periodontitis (2.25, 1.15-4.41), root canal fillings (1.15, 1.04-1.26), alveolar bone loss (2.66, 1.21-5.84), severe periodontal inflammation (2.23, 1.11-4.47), high level of gram-negative subgingival species (2.73, 1.34-5.50), saliva IgG against dysbiotic species (1.05, 1.01-1.10/unit) and severe (2.58, 1.36-4.90) and chronic (2.13, 1.15-3.93) CAD. A total of 105 (20.7%) patients died during the follow-up and 53 (10.4%) deaths were because of cardiovascular diseases (CVD). Severe CAC predicted worse survival with HRs (95% CI) of 3.08 (1.58-6.06) for all-cause and 3.43 (1.42-8.25) for CVD death. Conclusions CAC on panoramic tomography was associated with (i) apical and marginal periodontitis and dysbiotic bacterial species giving rise to an immunological response, and with (ii) severe, chronic CAD and increased mortality. The results further emphasize the role of oral infections in CAD and the importance of referring a patient with CAC for a cardiovascular evaluation.
  • Pokorney, Sean D.; Piccini, Jonathan P.; Stevens, Susanna R.; Patel, Manesh R.; Pieper, Karen S.; Halperin, Jonathan L.; Breithardt, Gunter; Singer, Daniel E.; Hankey, Graeme J.; Hacke, Werner; Becker, Richard C.; Berkowitz, Scott D.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.; ROCKET AF Steering Comm; Kaste, Markku (2016)
    Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereas
  • Finndiane Study Grp; Eriksson, Marika; Summanen, Paula; Gordin, Daniel; Forsblom, Carol; Shams, Sara; Liebkind, Ron; Tatlisumak, Turgut; Putaala, Jukka; Groop, Per-Henrik; Martola, Juha; Thorn, Lena M. (2021)
    Introduction Cerebral small-vessel disease is common in neurologically asymptomatic individuals with type 1 diabetes. The retinal vasculature is thought to mirror the brain's vasculature, but data on this association are limited in type 1 diabetes. Our aim was to study associations between diabetic retinopathy severity and cerebral small-vessel disease in type 1 diabetes. Research design and methods For this cross-sectional study, we enrolled 189 participants with type 1 diabetes (median age 40 (33-45) years; 53% female; diabetes duration 21.6 (18.2-30.7) years) and 29 healthy age-matched and sex-matched controls as part of the Finnish Diabetic Nephropathy Study. Participants underwent a clinical investigation, brain MRI, and fundus imaging. Signs of cerebral small-vessel disease in brain MRIs were analyzed in relation to diabetic retinopathy severity (Early Treatment Diabetic Retinopathy Study (ETDRS) score). Results In type 1 diabetes, participants with cerebral small-vessel disease had higher ETDRS scores (35 (20-61) vs 20 (20-35), p=0.022) and a higher prevalence of proliferative diabetic retinopathy than those without cerebral small-vessel disease (25% vs 9%, p=0.002). In adjusted analysis, proliferative diabetic retinopathy was associated with cerebral small-vessel disease (OR 2.57 (95% CI 1.04 to 6.35)). Median ETDRS score (35 (20-65) vs 20 (20-35), p=0.024) and proliferative diabetic retinopathy prevalence were higher (29% vs 13%, p=0.002) in participants with versus without cerebral microbleeds. ETDRS scores increased by number of cerebral microbleeds (p=0.001), both ETDRS score (OR 1.05 (95% CI 1.02 to 1.09)) and proliferative diabetic retinopathy (8.52 (95% CI 1.91 to 37.94)) were associated with >2 cerebral microbleeds in separate multivariable analysis. We observed no association with white matter hyperintensities or lacunar infarcts. Conclusions Presence of cerebral small-vessel disease on brain MRI, particularly cerebral microbleeds, is associated with the severity of diabetic retinopathy.
  • Thorn, Lena M.; Shams, Sara; Gordin, Daniel; Liebkind, Ron; Forsblom, Carol; Summanen, Paula; Hägg-Holmberg, Stefanie; Tatlisumak, Turgut; Salonen, Oili; Putaala, Jukka; Martola, Juha; Groop, Per-Henrik (2019)
    OBJECTIVETo assess the prevalence of cerebral small-vessel disease (SVD) in subjects with type 1 diabetes compared with healthy control subjects and to characterize the diabetes-related factors associated with SVD.RESEARCH DESIGN AND METHODSThis substudy was cross-sectional in design and included 191 participants with type 1 diabetes and median age 40.0 years (interquartile range 33.0-45.1) and 30 healthy age- and sex-matched control subjects. All participants underwent clinical investigation and brain MRIs, assessed for cerebral SVD.RESULTSCerebral SVD was more common in participants with type 1 diabetes than in healthy control subjects: any marker 35% vs. 10% (P = 0.005), cerebral microbleeds (CMBs) 24% vs. 3.3% (P = 0.008), white matter hyperintensities 17% vs. 6.7% (P = 0.182), and lacunes 2.1% vs. 0% (P = 1.000). Presence of CMBs was independently associated with systolic blood pressure (odds ratio 1.03 [95% CI 1.00-1.05], P = 0.035).CONCLUSIONSCerebral SVD, CMBs in particular, is more common in young people with type 1 diabetes compared with healthy control subjects.
  • Ristagno, Giuseppe; Latini, Roberto; Plebani, Mario; Zaninotto, Martina; Vaahersalo, Jukka; Masson, Serge; Tiainen, Marjaana; Kurola, Jouni; Gaspari, Flavio; Milani, Valentina; Pettila, Ville; Skrifvars, Markus Benedikt; FINNRESUSCI Study Grp (2015)
    Introduction: We studied associations of the stress hormones copeptin and cortisol with outcome and organ dysfunction after out-of-hospital cardiac arrest (OHCA). Methods: Plasma was obtained after consent from next of kin in the FINNRESUSCI study conducted in 21 Finnish intensive care units (ICUs) between 2010 and 2011. We measured plasma copeptin (pmol/L) and free cortisol (nmol/L) on ICU admission (245 patients) and at 48 hours (additional 33 patients). Organ dysfunction was categorised with 24-hour Sequential Organ Failure Assessment (SOFA) scores. Twelve-month neurological outcome (available in 276 patients) was classified with cerebral performance categories (CPC) and dichotomised into good (CPC 1 or 2) or poor (CPC 3 to 5). Data are presented as medians and interquartile ranges (IQRs). A Mann-Whitney U test, multiple linear and logistic regression tests with odds ratios (ORs) 95% confidence intervals (CIs) and beta (B) values, repeated measure analysis of variance, and receiver operating characteristic curves with area under the curve (AUC) were performed. Results: Patients with a poor 12-month outcome had higher levels of admission copeptin (89, IQR 41 to 193 versus 51, IQR 29 to 111 pmol/L, P = 0.0014) and cortisol (728, IQR 522 to 1,017 versus 576, IQR 355 to 850 nmol/L, P = 0.0013). Copeptin levels fell between admission and 48 hours (P Conclusions: Admission copeptin and free cortisol were not of prognostic value regarding 12-month neurological outcome after OHCA. Higher admission copeptin and cortisol were associated with ICU death, and copeptin predicted subsequent organ dysfunction.
  • Steele, Catriona M.; Mukherjee, Rajat; Kortelainen, Juha M.; Polonen, Harri; Jedwab, Michael; Brady, Susan L.; Theimer, Kayla Brinkman; Langmore, Susan; Riquelme, Luis F.; Swigert, Nancy B.; Bath, Philip M.; Goldstein, Larry B.; Hughes, Richard L.; Leifer, Dana; Lees, Kennedy R.; Meretoja, Atte; Muehlemann, Natalia (2019)
    Oropharyngeal dysphagia is prevalent in several at-risk populations, including post-stroke patients, patients in intensive care and the elderly. Dysphagia contributes to longer hospital stays and poor outcomes, including pneumonia. Early identification of dysphagia is recommended as part of the evaluation of at-risk patients, but available bedside screening tools perform inconsistently. In this study, we developed algorithms to detect swallowing impairment using a novel accelerometer-based dysphagia detection system (DDS). A sample of 344 individuals was enrolled across seven sites in the United States. Dual-axis accelerometry signals were collected prospectively with simultaneous videofluoroscopy (VFSS) during swallows of liquid barium stimuli in thin, mildly, moderately and extremely thick consistencies. Signal processing classifiers were trained using linear discriminant analysis and 10,000 random training-test data splits. The primary objective was to develop an algorithm to detect impaired swallowing safety with thin liquids with an area under receiver operating characteristic curve (AUC) > 80% compared to the VFSS reference standard. Impaired swallowing safety was identified in 7.2% of the thin liquid boluses collected. At least one unsafe thin liquid bolus was found in 19.7% of participants, but participants did not exhibit impaired safety consistently. The DDS classifier algorithms identified participants with impaired thin liquid swallowing safety with a mean AUC of 81.5%, (sensitivity 90.4%, specificity 60.0%). Thicker consistencies were effective for reducing the frequency of penetration-aspiration. This DDS reached targeted performance goals in detecting impaired swallowing safety with thin liquids. Simultaneous measures by DDS and VFSS, as performed here, will be used for future validation studies.
  • Särkamö, Teppo; Altenmueller, Eckart; Rodriguez-Fornells, Antoni; Peretz, Isabelle (2016)
  • Islam, Md. Zahirul; Shamim, Abu Ahmed; Akhtaruzzaman, Mohammad; Karkkainen, Merja; Lamberg-Allardt, Christel (2014)
    Elevated total cholesterol and low-density lipoprotein cholesterol in sera are both well-known risk factors of coronary heart disease. Adequate vitamin D status is important for optimal function of many organs and tissues of our body. There is continuing controversy about the effect of adequate vitamin D consumption on serum lipids and lipoproteins. The present study assessed the effect of vitamin D, calcium and multiple micronutrients supplementation on the lipid profile in Bangladeshi young female garment factory workers who have hypovitaminosis D. This placebo-controlled intervention trial conducted over a period of one year randomly assigned a total of 200 apparently healthy subjects aged 16-36 years to 4 groups. The subjects received daily supplements of 400 IU of vitamin D (VD group) or 400 IU of vitamin D+ 600 mg of calcium lactate (VD-Ca group), or multiple micronutrients with 400 IU of vitamin-D+ 600 mg of calcium lactate (MMN-VD-Ca group), or the group consuming placebo (PL group). Serum concentrations of lipid and lipoprotein, 25-hydroxyvitamin D (25OHD) and intact parathyroid hormone (iPTH) were measured at baseline and after one year of follow-up. No significant changes in the serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), LDL-C/HDL-C ratio were observed in the supplemented groups compared to the placebo group. Supplementation had a positive effect (p<0.05) on very low-density lipoprotein cholesterol (VLDL-C) and triacylglycerol (TAG). A negative correlation between changes in serum iPTH and HDL-C was observed, which indicated that subjects with the greatest decline in S-iPTH had the greatest increase in HDL-C. The results suggest that consumption of adequate vitamin D with calcium or MMN for one-year may have no impact on serum lipid profile in the subjects studied. Longer-term clinical trials with different doses of supplemental vitamin D are warranted in evaluating the effect of intervention.
  • Hartikainen, Sanna; Lipponen, Jukka A.; Hiltunen, Pamela; Rissanen, Tuomas T.; Kolk, Indrek; Tarvainen, Mika P.; Martikainen, Tero J.; Castren, Maaret; Väliaho, Eemu-Samuli; Jäntti, Helena (2019)
    Atrial fibrillation (AF) is a significant cause of cardioembolic strokes. AF is often symptomless and intermittent, making its detection challenging. The aim of this study was to assess the possibility to use a chest strap (Suunto Movesense) to detect AF both by cardiologists and automated algorithms. A single channel electrocardiogram (ECG) from a chest strap of 220 patients (107 AF and 111 sinus rhythm SR with 2 inconclusive rhythms) were analyzed by 2 cardiologists (Doc1 and Doc2) and 2 different algorithms (COSEn and AFE-vidence). A 3-lead Holter served as the gold standard ECG for rhythm analysis. Both cardiologists evaluated the quality of the chest strap ECG to be superior to the quality of the Holter ECG; p
  • Laakso, H. M.; Hietanen, M.; Melkas, S.; Sibolt, G.; Curtze, S.; Virta, M.; Ylikoski, R.; Pohjasvaara, T.; Kaste, M.; Erkinjuntti, T.; Jokinen, H. (2019)
    Background and purposeImpairment of executive functions (EFs) is a common cognitive symptom post-stroke and affects independence in daily activities. Previous studies have often relied on brief cognitive tests not fully considering the wide spectrum of EF subdomains. A detailed assessment of EFs was used to examine which of the subdomains and tests have the strongest predictive value on post-stroke functional outcome and institutionalization in long-term follow-up. MethodsA subsample of 62 patients from the Helsinki Stroke Aging Memory Study was evaluated with a battery of seven neuropsychological EF tests 3 months post-stroke and compared to 39 healthy control subjects. Functional impairment was evaluated with the modified Rankin Scale (mRS) and Instrumental Activities of Daily Living (IADL) scale at 3 months, and with the mRS at 15 months post-stroke. Institutionalization was reviewed from the national registers of permanent hospital admissions in up to 21-year follow-up. ResultsThe stroke group performed more poorly than the control group in multiple EF tests. Tests of inhibition, set shifting, initiation, strategy formation and processing speed were associated with the mRS and IADL scale in stroke patients. EF subdomain scores of inhibition, set shifting and processing speed were associated with functional outcome. In addition, inhibition was associated with the risk for earlier institutionalization. ConclusionsExecutive function was strongly associated with post-stroke functional impairment. In follow-up, poor inhibition was related to earlier permanent institutionalization. The results suggest the prognostic value of EF subdomains after stroke.
  • Zhao, Huiying; Eising, Else; de Vries, Boukje; Vijfhuizen, Lisanne S.; Anttila, Verneri; Winsvold, Bendik S.; Kurth, Tobias; Stefansson, Hreinn; Kallela, Kaarlo Mikko; Malik, Rainer; Stam, Anine H.; Ikram, M. Arfan; Ligthart, Lannie; Freilinger, Tobias; Alexander, Michael; Mueller-Myhsok, Bertram; Schreiber, Stefan; Meitinger, Thomas; Aromas, Arpo; Eriksson, Johan G.; Boomsma, Dorret I.; van Duijn, Cornelia M.; Zwart, John-Anker; Quaye, Lydia; Kubisch, Christian; Dichgans, Martin; Wessman, Maija; Stefansson, Kari; Chasman, Daniel I.; Palotie, Aarno; Martin, Nicholas G.; Montgomery, Grant W.; Ferrari, Michel D.; Terwindt, Gisela M.; van den Maagdenberg, Arn M. J. M.; Nyholt, Dale R.; Int Headache Genetics Consortium (2016)
    Introduction It is unclear whether patients diagnosed according to International Classification of Headache Disorders criteria for migraine with aura (MA) and migraine without aura (MO) experience distinct disorders or whether their migraine subtypes are genetically related. Aim Using a novel gene-based (statistical) approach, we aimed to identify individual genes and pathways associated both with MA and MO. Methods Gene-based tests were performed using genome-wide association summary statistic results from the most recent International Headache Genetics Consortium study comparing 4505 MA cases with 34,813 controls and 4038 MO cases with 40,294 controls. After accounting for non-independence of gene-based test results, we examined the significance of the proportion of shared genes associated with MA and MO. Results We found a significant overlap in genes associated with MA and MO. Of the total 1514 genes with a nominally significant gene-based p value (p(gene-based)0.05) in the MA subgroup, 107 also produced p(gene-based)0.05 in the MO subgroup. The proportion of overlapping genes is almost double the empirically derived null expectation, producing significant evidence of gene-based overlap (pleiotropy) (p(binomial-test) = 1.5x10(-4)). Combining results across MA and MO, six genes produced genome-wide significant gene-based p values. Four of these genes (TRPM8, UFL1, FHL5 and LRP1) were located in close proximity to previously reported genome-wide significant SNPs for migraine, while two genes, TARBP2 and NPFF separated by just 259bp on chromosome 12q13.13, represent a novel risk locus. The genes overlapping in both migraine types were enriched for functions related to inflammation, the cardiovascular system and connective tissue. Conclusions Our results provide novel insight into the likely genes and biological mechanisms that underlie both MA and MO, and when combined with previous data, highlight the neuropeptide FF-amide peptide encoding gene (NPFF) as a novel candidate risk gene for both types of migraine.
  • Lempiäinen, Juha; Ijäs, Petra; Niiranen, Teemu J.; Kaste, Markku; Karhunen, Pekka J.; Lindsberg, Perttu J.; Erkinjuntti, Timo; Melkas, Susanna (2020)
    Haptoglobin (Hp) is a plasma protein that binds free hemoglobin and protects tissues from oxidative damage. An Hp2 allele has been associated with an increased risk of cardiovascular complications. On the other hand, recent studies have suggested that Hp1 allele increases risk to develop severe cerebral small vessel disease. We aimed to replicate this finding in a first-ever stroke patient cohort. Hp was genotyped by PCR and gel electrophoresis in the Helsinki Stroke Aging Memory Study in patients with DNA and magnetic resonance imaging (MRI) available (SAM; n = 316). Lacunar infarcts and white matter lesions (WML) classified by Fazekas grading from brain MRI were associated with Hp genotypes. As population controls, we used participants of Cardiovascular diseases-a sub study of Health 2000 Survey (n = 1417). In the SAM cohort, 63.0% of Hp1-1 carriers (n = 46), 52.5% of Hp1-2 carriers (n = 141) and 51.2% of Hp2-2 carriers (n = 129) had severe WML (p = 0.372). There was no difference in severe WMLs between Hp1-1 vs. Hp1-2 and Hp2-2 carriers (p = 0.201). In addition, 68.9% of Hp1-1 carriers (n = 45), 58.5% of Hp1-2 carriers (n = 135), and 61.8% of Hp2-2 carriers (n = 126) had one or more lacunar lesions (p = 0.472). There was no difference in the number of patients with at least one lacunar infarct between Hp1-1 vs. Hp1-2 and Hp2-2 groups (p = 0.322). Neither was there any difference when diabetic patients (type I and II) were examined separately. Hp1 allele is not associated with an increased risk for cerebral small vessel disease in a well-characterized Finnish stroke patient cohort.
  • Litwin, Linda; Sundholm, Johnny K. M.; Meinilä, Jelena; Kulmala, Janne; Tammelin, Tuija H.; Rönö, Kristiina; Koivusalo, Saila B.; Eriksson, Johan G.; Sarkola, Taisto (2021)
    Background: Heredity and family-shared lifestyle contribute to cardiovascular risk, but the magnitude of their influence on arterial structure and function in early childhood is unknown. We aimed to assess associations between child and maternal ideal cardiovascular health, maternal subclinical atherosclerosis, and child arterial phenotype. Methods: Cross-sectional analysis of 201 mother-child pairs originating from the Finnish Gestational Diabetes Prevention Study (RADIEL) longitudinal cohort was done at child age 6.1 +/- 0.5 years with assessments of ideal cardiovascular health (BMI, blood pressure, fasting glucose, total cholesterol, diet quality, physical activity, smoking), body composition, very-high frequency ultrasound of carotid arteries (25 and 35 MHz), and pulse wave velocity. Results: We found no association between child and maternal ideal cardiovascular health but report evidence of particular metrics correlations: total cholesterol (r=0.24, P=0.003), BMI (r=0.17, P=0.02), diastolic blood pressure (r=0.15, P=0.03), and diet quality (r=0.22, P=0.002). Child arterial phenotype was not associated with child or maternal ideal cardiovascular health. In the multivariable regression explanatory model adjusted for child sex, age, systolic blood pressure, lean body mass, and body fat percentage, child carotid intima-media thickness was independently associated only with maternal carotid intima-media thickness (0.1 mm increase [95% CI 0.05, 0.21, P=0.001] for each 1 mm increase in maternal carotid intima-media thickness). Children of mothers with subclinical atherosclerosis had decreased carotid artery distensibility (1.1 +/- 0.2 vs 1.2 +/- 0.2%/10 mmHg, P=0.01) and trend toward increased carotid intima-media thickness (0.37 +/- 0.04 vs 0.35 +/- 0.04 mm, P=0.06). Conclusion: Ideal Cardiovascular Health metrics are heterogeneously associated in mother-child pairs in early childhood. We found no evidence of child or maternal Ideal Cardiovascular Health effect on child arterial phenotype. Maternal carotid intima-media thickness predicts child carotid intima-media thickness, but the underlying mechanisms remain unclear. Maternal subclinical atherosclerosis is associated with local carotid arterial stiffness in early childhood.
  • Lahti, Anna-Maija; Huhtakangas, Juha; Juvela, Seppo; Bode, Michaela K.; Tetri, Sami (2021)
    Objectives: This study aimed to determine whether post-stroke epilepsy (PSE) predicts mortality, and to describe the most prominent causes of death (COD) in a long-term follow-up after primary intracerebral hemorrhage (ICH). Methods: We followed 3-month survivors of a population-based cohort of primary ICH patients in Northern Ostrobothnia, Finland, for a median of 8.8 years. Mortality and CODs were compared between those who developed PSE and those who did not. PSE was defined according to the ILAE guidelines. CODs were extracted from death certificates (Statistics Finland). Results: Of 961 patients, 611 survived for 3 months. 409 (66.9%) had died by the end of the follow-up. Pneumonia was the only COD that was significantly more common among the patients with PSE (56% vs. 37% of deaths). In the multivariable models, PSE (hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.06 & ndash;1.87), age (HR 1.07, 95% CI 1.06 & ndash;1.08), male sex (HR 1.35, 95% CI 1.09 & ndash;1.67), dependency at 3 months (HR 1.52, 95% CI 1.24 & ndash;1.88), non-subcortical ICH location (subcortical location HR 0.78, 95% CI 0.61-0.99), diabetes (HR 1.43, 95% CI 1.07 & ndash;1.90) and cancer (HR 1.45, 95% CI 1.06 & ndash;1.98) predicted death in the long-term follow-up. Conclusion: PSE independently predicted higher late morality of ICH in our cohort. Pneumonia-related deaths were more common among the patients with PSE.
  • Frosen, Juhana; Rezai Jahromi, Behnam; Hernesniemi, Juha (2016)
  • INTERACT2 Investigators; Kaste, Markku; Tatlisumak, Turgut (2017)
    Objective: To clarify associations between intracerebral hemorrhage (ICH) location and clinical outcomes among participants of the main phase Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). Methods: Associations between ICH sites and poor outcomes (death [6] or major disability [3-5] of modified Rankin Scale) and European Quality of Life Scale (EQ-5D) utility scores at 90 days were assessed in logistic regression models. Results: Of 2,066 patients included in the analyses, associations were identified between ICH sites and poor outcomes: involvement of posterior limb of internal capsule increased risks of death or major disability (odds ratio [OR] 2.10) and disability (OR 1.81); thalamic involvement increased risks of death or major disability (OR 2.24) and death (OR 1.97). Involvement of the posterior limb of the internal capsule, thalamus, and infratentorial sites were each associated with poor EQ-5D utility score ( Conclusion: Poor clinical outcomes are related to ICH affecting the posterior limb of internal capsule, thalamus, and infratentorial sites. The highest association with death or major disability and poor EQ-5D utility score was seen in ICH encompassing the thalamus and posterior limb of internal capsule.
  • Tolmacheva, Aleksandra; Savolainen, Sarianna; Kirveskari, Erika; Lioumis, Pantelis; Kuusela, Linda; Brandstack, Nina; Ylinen, Aarne; Mäkelä, Jyrki P.; Shulga, Anastasia (2017)
    A large proportion of spinal cord injuries (SCI) are incomplete. Even in clinically complete injuries, silent non-functional connections can be present. Therapeutic approaches that can strengthen transmission in weak neural connections to improve motor performance are needed. Our aim was to determine whether long-term delivery of paired associative stimulation (PAS, a combination of transcranial magnetic stimulation [TMS] with peripheral nerve stimulation [PNS]) can enhance motor output in the hands of patients with chronic traumatic tetraplegia, and to compare this technique with long-term PNS. Five patients (4 males; age 38-68, mean 48) with no contraindications to TMS received 4 weeks (16 sessions) of stimulation. PAS was given to one hand and PNS combined with sham TMS to the other hand. Patients were blinded to the treatment. Hands were selected randomly. The patients were evaluated by a physiotherapist blinded to the treatment. The follow-up period was 1 month. Patients were evaluated with Daniels and Worthingham's Muscle Testing (0-5 scale) before the first stimulation session, after the last stimulation session, and 1 month after the last stimulation session. One month after the last stimulation session, the improvement in the PAS-treated hand was 1.02 +/- 0.17 points (p <0.0001, n = 100 muscles from 5 patients). The improvement was significantly higher in PAS-treated than in PNS-treated hands (176 +/- 29%, p = 0.046, n = 5 patients). Longterm PAS might be an effective tool for improving motor performance in incomplete chronic SCI patients. Further studies on PAS in larger patient cohorts, with longer stimulation duration and at earlier stages after the injury, are warranted.