Risks associated with the stroke predisposition at young age: facts and hypotheses in light of individualized predictive and preventive approach
Status PubMed-not-MEDLINE Jazyk angličtina Země Švýcarsko Médium electronic-ecollection
Typ dokumentu časopisecké články, přehledy
PubMed
30984317
PubMed Central
PMC6459458
DOI
10.1007/s13167-019-00162-5
PII: 162
Knihovny.cz E-zdroje
- Klíčová slova
- Abnormal BMI, Altered sensation, Baroreceptor sensitivity, Blood flow, Body dehydration, Cardiac, Circadian rhythm, Etiology, Flammer syndrome, Hormonal regulation, Individualized patient profile, Life style, Microcirculation, Migraine, Phenotype, Predictive preventive personalized medicine, Psychology, Questionnaire, Risk assessment, Risk factors, Screening program, Sleep patterns, Stress, Stroke, Thermoregulation, Tinnitus, Vascular, Young adults,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Stroke is one of the most devastating pathologies of the early twenty-first century demonstrating 1-month case-fatality rates ranging from 13 to 35% worldwide. Though the majority of cases do occur in individuals at an advanced age, a persistently increasing portion of the patient cohorts is affected early in life. Current studies provide alarming statistics for the incidence of "young" strokes including adolescents. Young stroke is a multifactorial disease involving genetic predisposition but also a number of modifiable factors, the synergic combination of which potentiates the risks. The article analyzes the prevalence and impacts of "traditional" risk factors such as sedentary lifestyle, smoking, abnormal alcohol consumption, drug abuse, overweight, hypertension, abnormal sleep patterns, and usage of hormonal contraceptives, among others. Further, less explored risks such as primary vascular dysregulation and associated symptoms characteristic for Flammer syndrome (FS) are considered, and the relevance of the FS phenotype for the stroke predisposition at young age is hypothesized. Considering the high prevalence of known genetic and modifiable risk factors in the overall predisposition to the young stroke, the risk mitigating measures are recommended including innovative screening programs by application of specialized questionnaires and biomarker panels as well as educational programs adapted to the target audiences such as children, adolescents, and young adults.
Biomedical Centre Faculty of Medicine in Pilsen Charles University Staré Město Czech Republic
Breast Cancer Research Centre UKB Rheinische Friedrich Wilhelms Universität Bonn Bonn Germany
CEMBIO University of Bonn Bonn Germany
Department of Biology Faculty of Medicine in Pilsen Charles University Staré Město Czech Republic
Department of Immunochemistry University Hospital Pilsen Pilsen Czech Republic
Zobrazit více v PubMed
Johnston SC, Mendis S, Mathers CD. Global variation in stroke burden and mortality: estimates from monitoring, surveillance, and modelling. Lancet Neurol. 2009;8:345–354. PubMed
Béjot Y, Bailly H, Durier J, Giroud M. Epidemiology of stroke in Europe and trends for the 21st century. Presse Med. 2016;45:e391–e398. PubMed
Polivka J, Polivka J, Rohan V. Predictive and individualized management of stroke—success story in Czech Republic. EPMA J. 2018;9:393–401. PubMed PMC
Maaijwee NAMM, Rutten-Jacobs LCA, Schaapsmeerders P, van Dijk EJ, de Leeuw F-E. Ischaemic stroke in young adults: risk factors and long-term consequences. Nat Rev Neurol. 2014;10:315–325. PubMed
Béjot Y, Delpont B, Giroud M. Rising stroke incidence in young adults: more epidemiological evidence, more questions to be answered. J Am Heart Assoc. 2016;5. PubMed PMC
Aigner A, Grittner U, Rolfs A, Norrving B, Siegerink B, Busch MA. Contribution of established stroke risk factors to the burden of stroke in young adults. Stroke. 2017;48:1744–1751. PubMed
von Sarnowski B, Putaala J, Grittner U, Gaertner B, Schminke U, Curtze S, Huber R, Tanislav C, Lichy C, Demarin V, Basic-Kes V, Ringelstein EB, Neumann-Haefelin T, Enzinger C, Fazekas F, Rothwell PM, Dichgans M, Jungehulsing GJ, Heuschmann PU, Kaps M, Norrving B, Rolfs A, Kessler C, Tatlisumak T. Lifestyle risk factors for ischemic stroke and transient ischemic attack in young adults in the stroke in young Fabry patients study. Stroke. 2013;44:119–125. PubMed
Goeggel Simonetti B, Mono M-L, Huynh-Do U, Michel P, Odier C, Sztajzel R, Lyrer P, Engelter ST, Bonati L, Gensicke H, Traenka C, Tettenborn B, Weder B, Fischer U, Galimanis A, Jung S, Luedi R, de Marchis GM, Weck A, Cereda CW, Baumgartner R, Bassetti CL, Mattle HP, Nedeltchev K, Arnold M. Risk factors, aetiology and outcome of ischaemic stroke in young adults: the Swiss young stroke study (SYSS) J Neurol. 2015;262:2025–2032. PubMed
Leung LY, Caplan LR. Factors associated with delay in presentation to the hospital for young adults with ischemic stroke. Cerebrovasc Dis. 2016;42:10–14. PubMed
Polivka J, Krakorova K, Peterka M, Topolcan O. Current status of biomarker research in neurology. EPMA J. 2016;7:14. PubMed PMC
Polívka J, Rohan V, Sevčík P, Polívka J. Personalized approach to primary and secondary prevention of ischemic stroke. EPMA J. 2014;5:9. PubMed PMC
Tatlisumak T, Cucchiara B, Kuroda S, Kasner SE, Putaala J. Nontraumatic intracerebral haemorrhage in young adults. Nat Rev Neurol. 2018;14:237–250. PubMed
Ji R, Schwamm LH, Pervez MA, Singhal AB. Ischemic stroke and transient ischemic attack in young adults: risk factors, diagnostic yield, neuroimaging, and thrombolysis. JAMA Neurol. 2013;70:51–57. PubMed
Kwon SU, Kim JS, Lee JH, Lee MC. Ischemic stroke in Korean young adults. Acta Neurol Scand. 2000;101:19–24. PubMed
de los Ríos F, Kleindorfer DO, Khoury J, Broderick JP, Moomaw CJ, Adeoye O, et al. Trends in substance abuse preceding stroke among young adults: a population-based study. Stroke. 2012;43:3179–3183. PubMed PMC
Yesilot Barlas N, Putaala J, Waje-Andreassen U, Vassilopoulou S, Nardi K, Odier C, Hofgart G, Engelter S, Burow A, Mihalka L, Kloss M, Ferrari J, Lemmens R, Coban O, Haapaniemi E, Maaijwee N, Rutten-Jacobs L, Bersano A, Cereda C, Baron P, Borellini L, Valcarenghi C, Thomassen L, Grau AJ, Palm F, Urbanek C, Tuncay R, Durukan Tolvanen A, van Dijk E, de Leeuw FE, Thijs V, Greisenegger S, Vemmos K, Lichy C, Bereczki D, Csiba L, Michel P, Leys D, Spengos K, Naess H, Tatlisumak T, Bahar SZ. Etiology of first-ever ischaemic stroke in European young adults: the 15 cities young stroke study. Eur J Neurol. 2013;20:1431–1439. PubMed
Mallick AA, Ganesan V, Kirkham FJ, Fallon P, Hedderly T, McShane T, Parker AP, Wassmer E, Wraige E, Amin S, Edwards HB, Tilling K, O'Callaghan FJ. Childhood arterial ischaemic stroke incidence, presenting features, and risk factors: a prospective population-based study. Lancet Neurol. 2014;13:35–43. PubMed
Gerstl L, Weinberger R, von Kries R, Heinen F, Schroeder AS, Bonfert MV, Borggraefe I, Tacke M, Vill K, Landgraf MN, Kurnik K, Olivieri M. Risk factors in childhood arterial ischaemic stroke: findings from a population-based study in Germany. Eur J Paediatr Neurol. 2018;22:380–386. PubMed
Riel-Romero RMS, Kalra AA, Gonzalez-Toledo E. Childhood and teenage stroke. Neurol Res. 2009;31:775–784. PubMed
Riel-Romero RMS. Neonatal stroke. Neurol Res. 2008;30:839–844. PubMed
Adams HP, Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE., 3rd Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of org 10172 in acute stroke treatment. Stroke. 1993;24:35–41. PubMed
Schneider S, Kornejeva A, Vibo R, Kõrv J. Risk factors and etiology of young ischemic stroke patients in Estonia. Stroke Res Treat. 2017;2017:8075697. PubMed PMC
Kissela BM, Khoury JC, Alwell K, Moomaw CJ, Woo D, Adeoye O, Flaherty ML, Khatri P, Ferioli S, de Los Rios la Rosa F, Broderick JP, Kleindorfer DO. Age at stroke: temporal trends in stroke incidence in a large, biracial population. Neurology. 2012;79:1781–1787. PubMed PMC
George MG, Tong X, Kuklina EV, Labarthe DR. Trends in stroke hospitalizations and associated risk factors among children and young adults, 1995-2008. Ann Neurol. 2011;70:713–721. PubMed
Béjot Y, Daubail B, Jacquin A, Durier J, Osseby G-V, Rouaud O, et al. Trends in the incidence of ischaemic stroke in young adults between 1985 and 2011: the Dijon stroke registry. J Neurol Neurosurg Psychiatry. 2014;85:509–513. PubMed
Medin J, Nordlund A, Ekberg K. Swedish Hospital Discharge Register. Increasing stroke incidence in Sweden between 1989 and 2000 among persons aged 30 to 65 years: evidence from the Swedish Hospital Discharge Register. Stroke. 2004;35:1047–1051. PubMed
Ramirez L, Kim-Tenser MA, Sanossian N, Cen S, Wen G, He S, et al. Trends in acute ischemic stroke hospitalizations in the United States. J Am Heart Assoc. 2016;5. PubMed PMC
Tibæk M, Dehlendorff C, Jørgensen HS, Forchhammer HB, Johnsen SP, Kammersgaard LP. Increasing incidence of hospitalization for stroke and transient ischemic attack in young adults: a registry-based study. J Am Heart Assoc. 2016;5. PubMed PMC
Cabral NL, Freire AT, Conforto AB, Dos Santos N, Reis FI, Nagel V, et al. Increase of stroke incidence in young adults in a middle-income country: a 10-year population-based study. Stroke. 2017;48:2925–2930. PubMed
Ning X, Sun J, Jiang R, Lu H, Bai L, Shi M, Tu J, Wu Y, Wang J, Zhang J. Increased stroke burdens among the low-income young and middle aged in rural China. Stroke. 2017;48:77–83. PubMed
Maredza M, Bertram MY, Tollman SM. Disease burden of stroke in rural South Africa: an estimate of incidence, mortality and disability adjusted life years. BMC Neurol. 2015;15:54. PubMed PMC
Sarfo FS, Ovbiagele B, Gebregziabher M, Wahab K, Akinyemi R, Akpalu A, Akpa O, Obiako R, Owolabi L, Jenkins C, Owolabi M, SIREN Stroke among young west Africans: evidence from the SIREN (stroke investigative research and educational network) large multisite case-control study. Stroke. 2018;49:1116–1122. PubMed PMC
Ferro JM, Massaro AR, Mas J-L. Aetiological diagnosis of ischaemic stroke in young adults. Lancet Neurol. 2010;9:1085–1096. PubMed
Berghöfer A, Pischon T, Reinhold T, Apovian CM, Sharma AM, Willich SN. Obesity prevalence from a European perspective: a systematic review. BMC Public Health. 2008;8:200. PubMed PMC
Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27:1047–1053. PubMed
Wijnhoven TMA, van Raaij JMA, Spinelli A, Rito AI, Hovengen R, Kunesova M, Starc G, Rutter H, Sjöberg A, Petrauskiene A, O'Dwyer U, Petrova S, Farrugia Sant'Angelo V, Wauters M, Yngve A, Rubana IM, Breda J. WHO European childhood obesity surveillance initiative 2008: weight, height and body mass index in 6-9-year-old children. Pediatr Obes. 2013;8:79–97. PubMed
O’Donnell MJ, Chin SL, Rangarajan S, Xavier D, Liu L, Zhang H, et al. Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study. Lancet. 2016;388:761–775. PubMed
Terni E, Giannini N, Brondi M, Montano V, Bonuccelli U, Mancuso M. Genetics of ischaemic stroke in young adults. BBA Clin. 2015;3:96–106. PubMed PMC
Jood K, Ladenvall P, Tjärnlund-Wolf A, Ladenvall C, Andersson M, Nilsson S, et al. Fibrinolytic gene polymorphism and ischemic stroke. Stroke. 2005;36:2077–2081. PubMed
Bevan S, Traylor M, Adib-Samii P, Malik R, Paul NLM, Jackson C, Farrall M, Rothwell PM, Sudlow C, Dichgans M, Markus HS. Genetic heritability of ischemic stroke and the contribution of previously reported candidate gene and genomewide associations. Stroke. 2012;43:3161–3167. PubMed
Falcone GJ, Malik R, Dichgans M, Rosand J. Current concepts and clinical applications of stroke genetics. Lancet Neurol. 2014;13:405–418. PubMed
Chauhan G, Debette S. Genetic risk factors for ischemic and hemorrhagic stroke. Curr Cardiol Rep. 2016;18:124. PubMed PMC
Yoneda M, Maeda M, Kimura H, Fujii A, Katayama K, Kuriyama M. Vasogenic edema on MELAS: a serial study with diffusion-weighted MR imaging. Neurology. 1999;53:2182–2184. PubMed
Goto Y, Horai S, Matsuoka T, Koga Y, Nihei K, Kobayashi M, Nonaka I. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS): a correlative study of the clinical features and mitochondrial DNA mutation. Neurology. 1992;42:545–550. PubMed
Kaufmann P, Engelstad K, Wei Y, Kulikova R, Oskoui M, Battista V, Koenigsberger DY, Pascual JM, Sano M, Hirano M, DiMauro S, Shungu DC, Mao X, de Vivo DC. Protean phenotypic features of the A3243G mitochondrial DNA mutation. Arch Neurol. 2009;66:85–91. PubMed PMC
Sharma P, Yadav S, Meschia JF. Genetics of ischaemic stroke. J Neurol Neurosurg Psychiatry. 2013;84:1302–1308. PubMed
Razvi SSM, Bone I. Single gene disorders causing ischaemic stroke. J Neurol. 2006;253:685–700. PubMed
Chabriat H, Joutel A, Dichgans M, Tournier-Lasserve E, Bousser M-G. Cadasil. Lancet Neurol. 2009;8:643–653. PubMed
Federico A, Di Donato I, Bianchi S, Di Palma C, Taglia I, Dotti MT. Hereditary cerebral small vessel diseases: a review. J Neurol Sci. 2012;322:25–30. PubMed
Masoli JAH, Pilling LC, Kuchel GA, Melzer D. Clinical outcomes of CADASIL-associated NOTCH3 mutations in 451,424 European ancestry community volunteers. Transl Stroke Res. 2018. PubMed PMC
Germain DP. Fabry disease. Orphanet J Rare Dis. 2010;5:30. PubMed PMC
Zarate YA, Hopkin RJ. Fabry’s disease. Lancet. 2008;372:1427–1435. PubMed
Toyooka K. Fabry disease. Curr Opin Neurol. 2011;24:463–468. PubMed
Körver S, Vergouwe M, Hollak CEM, van Schaik IN, Langeveld M. Development and clinical consequences of white matter lesions in Fabry disease: a systematic review. Mol Genet Metab. 2018;125:205–216. PubMed
Wald NJ, Law M, Haddow JE, Craig WY. Apolipoprotiens and prediction of fatal myocardial infarction. Lancet. 2002;359:1864. PubMed
Alluri RV, Mohan V, Komandur S, Chawda K, Chaudhuri JR, Hasan Q. MTHFR C677T gene mutation as a risk factor for arterial stroke: a hospital based study. Eur J Neurol. 2005;12:40–44. PubMed
Sarecka-Hujar B, Kopyta I, Pienczk-Reclawowicz K, Reclawowicz D, Emich-Widera E, Pilarska E. The TT genotype of methylenetetrahydrofolate reductase 677C>T polymorphism increases the susceptibility to pediatric ischemic stroke: meta-analysis of the 822 cases and 1,552 controls. Mol Biol Rep. 2012;39:7957–7963. PubMed PMC
Guo J, Liu A, Su D. Genetics of stroke. Acta Pharmacol Sin. 2010;31:1055–1064. PubMed PMC
Casas JP, Hingorani AD, Bautista LE, Sharma P. Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18,000 cases and 58,000 controls. Arch Neurol. 2004;61:1652–1661. PubMed
Bersano A, Ballabio E, Bresolin N, Candelise L. Genetic polymorphisms for the study of multifactorial stroke. Hum Mutat. 2008;29:776–795. PubMed
Linthorst GE, Bouwman MG, Wijburg FA, Aerts JMFG, Poorthuis BJHM, Hollak CEM. Screening for Fabry disease in high-risk populations: a systematic review. J Med Genet. 2010;47:217–222. PubMed
Hamedani AG, Cole JW, Mitchell BD, Kittner SJ. Meta-analysis of factor V Leiden and ischemic stroke in young adults: the importance of case ascertainment. Stroke. 2010;41:1599–1603. PubMed PMC
Ibrahim-Verbaas CA, Fornage M, Bis JC, Choi SH, Psaty BM, Meigs JB, Rao M, Nalls M, Fontes JD, O’Donnell CJ, Kathiresan S, Ehret GB, Fox CS, Malik R, Dichgans M, Schmidt H, Lahti J, Heckbert SR, Lumley T, Rice K, Rotter JI, Taylor KD, Folsom AR, Boerwinkle E, Rosamond WD, Shahar E, Gottesman RF, Koudstaal PJ, Amin N, Wieberdink RG, Dehghan A, Hofman A, Uitterlinden AG, DeStefano AL, Debette S, Xue L, Beiser A, Wolf PA, DeCarli C, Ikram MA, Seshadri S, Mosley TH, Jr, Longstreth WT, Jr, van Duijn CM, Launer LJ. Predicting stroke through genetic risk functions: the CHARGE risk score project. Stroke. 2014;45:403–412. PubMed PMC
Gudbjartsson DF, Arnar DO, Helgadottir A, Gretarsdottir S, Holm H, Sigurdsson A, Jonasdottir A, Baker A, Thorleifsson G, Kristjansson K, Palsson A, Blondal T, Sulem P, Backman VM, Hardarson GA, Palsdottir E, Helgason A, Sigurjonsdottir R, Sverrisson JT, Kostulas K, Ng MCY, Baum L, So WY, Wong KS, Chan JCN, Furie KL, Greenberg SM, Sale M, Kelly P, MacRae CA, Smith EE, Rosand J, Hillert J, Ma RCW, Ellinor PT, Thorgeirsson G, Gulcher JR, Kong A, Thorsteinsdottir U, Stefansson K. Variants conferring risk of atrial fibrillation on chromosome 4q25. Nature. 2007;448:353–357. PubMed
Lemmens R, Buysschaert I, Geelen V, Fernandez-Cadenas I, Montaner J, Schmidt H, Schmidt R, Attia J, Maguire J, Levi C, Jood K, Blomstrand C, Jern C, Wnuk M, Slowik A, Lambrechts D, Thijs V, International Stroke Genetics Consortium The association of the 4q25 susceptibility variant for atrial fibrillation with stroke is limited to stroke of cardioembolic etiology. Stroke. 2010;41:1850–1857. PubMed
International Stroke Genetics Consortium (ISGC) Wellcome Trust Case Control Consortium 2 (WTCCC2) Bellenguez C, Bevan S, Gschwendtner A, Spencer CCA, et al. Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke. Nat Genet. 2012;44:328–333. PubMed PMC
Traylor M, Farrall M, Holliday EG, Sudlow C, Hopewell JC, Cheng Y-C, Fornage M, Ikram MA, Malik R, Bevan S, Thorsteinsdottir U, Nalls MA, Longstreth W, Wiggins KL, Yadav S, Parati EA, Destefano AL, Worrall BB, Kittner SJ, Khan MS, Reiner AP, Helgadottir A, Achterberg S, Fernandez-Cadenas I, Abboud S, Schmidt R, Walters M, Chen WM, Ringelstein EB, O'Donnell M, Ho WK, Pera J, Lemmens R, Norrving B, Higgins P, Benn M, Sale M, Kuhlenbäumer G, Doney AS, Vicente AM, Delavaran H, Algra A, Davies G, Oliveira SA, Palmer CN, Deary I, Schmidt H, Pandolfo M, Montaner J, Carty C, de Bakker PI, Kostulas K, Ferro JM, van Zuydam N, Valdimarsson E, Nordestgaard BG, Lindgren A, Thijs V, Slowik A, Saleheen D, Paré G, Berger K, Thorleifsson G, Australian Stroke Genetics Collaborative, Wellcome Trust Case Control Consortium 2 (WTCCC2) Hofman A, Mosley TH, Mitchell BD, Furie K, Clarke R, Levi C, Seshadri S, Gschwendtner A, Boncoraglio GB, Sharma P, Bis JC, Gretarsdottir S, Psaty BM, Rothwell PM, Rosand J, Meschia JF, Stefansson K, Dichgans M, Markus HS, International Stroke Genetics Consortium Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration): a meta-analysis of genome-wide association studies. Lancet Neurol. 2012;11:951–962. PubMed PMC
Ikram MA, Seshadri S, Bis JC, Fornage M, DeStefano AL, Aulchenko YS, et al. Genomewide association studies of stroke. N Engl J Med. 2009;360:1718–1728. PubMed PMC
Traylor M, Mäkelä K-M, Kilarski LL, Holliday EG, Devan WJ, Nalls MA, Wiggins KL, Zhao W, Cheng YC, Achterberg S, Malik R, Sudlow C, Bevan S, Raitoharju E, METASTROKE, International Stroke Genetics Consortium, Wellcome Trust Case Consortium 2 (WTCCC2) Oksala N, Thijs V, Lemmens R, Lindgren A, Slowik A, Maguire JM, Walters M, Algra A, Sharma P, Attia JR, Boncoraglio GB, Rothwell PM, de Bakker PIW, Bis JC, Saleheen D, Kittner SJ, Mitchell BD, Rosand J, Meschia JF, Levi C, Dichgans M, Lehtimäki T, Lewis CM, Markus HS. A novel MMP12 locus is associated with large artery atherosclerotic stroke using a genome-wide age-at-onset informed approach. PLoS Genet. 2014;10:e1004469. PubMed PMC
Rutten-Jacobs LCA, Maaijwee NAM, Arntz RM, Schoonderwaldt HC, Dorresteijn LD, van der Vlugt MJ, van Dijk EJ, de Leeuw FE. Long-term risk of recurrent vascular events after young stroke: the FUTURE study. Ann Neurol. 2013;74:592–601. PubMed
Putaala J, Haapaniemi E, Kaste M, Tatlisumak T. How does number of risk factors affect prognosis in young patients with ischemic stroke? Stroke. 2012;43:356–361. PubMed
Li F, Yang L, Yang R, Xu W, Chen F-P, Li N, Zhang JB. Ischemic stroke in young adults of northern China: characteristics and risk factors for recurrence. Eur Neurol. 2017;77:115–122. PubMed PMC
Renna R, Pilato F, Profice P, Della Marca G, Broccolini A, Morosetti R, Frisullo G, Rossi E, de Stefano V, di Lazzaro V. Risk factor and etiology analysis of ischemic stroke in young adult patients. J Stroke Cerebrovasc Dis. 2014;23:e221–e227. PubMed
Montanaro VVA, Freitas DDS, Ruiz MCM, Cavalcanti EBU, Marinho PBC, Freitas MCDNB, et al. Ischemic stroke in young adults: profile of SARAH Hospital Brasília from 2008 to 2012. Neurologist. 2017;22:61–63. PubMed
Mitchell AB, Cole JW, McArdle PF, Cheng Y-C, Ryan KA, Sparks MJ, et al. Obesity increases risk of ischemic stroke in young adults. Stroke. 2015;46:1690–1692. PubMed PMC
Park D, Lee J-H, Han S. Underweight: another risk factor for cardiovascular disease?: a cross-sectional 2013 Behavioral Risk Factor Surveillance System (BRFSS) study of 491,773 individuals in the USA. Medicine (Baltimore) 2017;96:e8769. PubMed PMC
Cui R, Iso H, Toyoshima H, Date C, Yamamoto A, Kikuchi S, Kondo T, Watanabe Y, Koizumi A, Wada Y, Inaba Y, Tamakoshi A, JACC Study Group Body mass index and mortality from cardiovascular disease among Japanese men and women: the JACC study. Stroke. 2005;36:1377–1382. PubMed
Markidan J, Cole JW, Cronin CA, Merino JG, Phipps MS, Wozniak MA, Kittner SJ. Smoking and risk of ischemic stroke in young men. Stroke. 2018;49:1276–1278. PubMed PMC
Bhat VM, Cole JW, Sorkin JD, Wozniak MA, Malarcher AM, Giles WH, Stern BJ, Kittner SJ. Dose-response relationship between cigarette smoking and risk of ischemic stroke in young women. Stroke. 2008;39:2439–2443. PubMed PMC
Magee CA, Kritharides L, Attia J, McElduff P, Banks E. Short and long sleep duration are associated with prevalent cardiovascular disease in Australian adults. J Sleep Res. 2012;21:441–447. PubMed
Sloan MA, Kittner SJ, Feeser BR, Gardner J, Epstein A, Wozniak MA, Wityk RJ, Stern BJ, Price TR, Macko RF, Johnson CJ, Earley CJ, Buchholz D. Illicit drug-associated ischemic stroke in the Baltimore-Washington young stroke study. Neurology. 1998;50:1688–1693. PubMed
Wolff V, Lauer V, Rouyer O, Sellal F, Meyer N, Raul JS, Sabourdy C, Boujan F, Jahn C, Beaujeux R, Marescaux C. Cannabis use, ischemic stroke, and multifocal intracranial vasoconstriction: a prospective study in 48 consecutive young patients. Stroke. 2011;42:1778–1780. PubMed
Westover AN, McBride S, Haley RW. Stroke in young adults who abuse amphetamines or cocaine: a population-based study of hospitalized patients. Arch Gen Psychiatry. 2007;64:495–502. PubMed
Roach REJ, Helmerhorst FM, Lijfering WM, Stijnen T, Algra A, Dekkers OM. Combined oral contraceptives: the risk of myocardial infarction and ischemic stroke. Cochrane Database Syst Rev. 2015:CD011054. PubMed PMC
Plu-Bureau G, Hugon-Rodin J, Maitrot-Mantelet L, Canonico M. Hormonal contraceptives and arterial disease: an epidemiological update. Best Pract Res Clin Endocrinol Metab. 2013;27:35–45. PubMed
Ban L, Sprigg N, Abdul Sultan A, Nelson-Piercy C, Bath PM, Ludvigsson JF, et al. Incidence of first stroke in pregnant and nonpregnant women of childbearing age: a population-based cohort study from England. J Am Heart Assoc. 2017;6. PubMed PMC
Maino A, Siegerink B, Algra A, Martinelli I, Peyvandi F, Rosendaal FR. Pregnancy loss and risk of ischaemic stroke and myocardial infarction. Br J Haematol. 2016;174:302–309. PubMed
González-Gómez FJ, Pérez-Torre P, DeFelipe A, Vera R, Matute C, Cruz-Culebras A, Álvarez-Velasco R, Masjuan J. Stroke in young adults: incidence rate, risk factors, treatment and prognosis. Rev Clin Esp. 2016;216:345–351. PubMed
Lightbody CE, Clegg A, Patel K, Lucas JC, Storey H, Hackett ML, Watkins DCL. Systematic review and meta-analysis of psychosocial risk factors for stroke. Semin Neurol. 2017;37:294–306. PubMed
Pistoia F, Sacco S, Degan D, Tiseo C, Ornello R, Carolei A. Hypertension and stroke: epidemiological aspects and clinical evaluation. High Blood Press Cardiovasc Prev. 2016;23:9–18. PubMed
Seshadri S, Beiser A, Kelly-Hayes M, Kase CS, Au R, Kannel WB, Wolf PA. The lifetime risk of stroke: estimates from the Framingham study. Stroke. 2006;37:345–350. PubMed
Turin TC, Okamura T, Afzal AR, Rumana N, Watanabe M, Higashiyama A, Nakao Y, Nakai M, Takegami M, Nishimura K, Kokubo Y, Okayama A, Miyamoto Y. Hypertension and lifetime risk of stroke. J Hypertens. 2016;34:116–122. PubMed
Allen N, Berry JD, Ning H, Van Horn L, Dyer A, Lloyd-Jones DM. Impact of blood pressure and blood pressure change during middle age on the remaining lifetime risk for cardiovascular disease: the cardiovascular lifetime risk pooling project. Circulation. 2012;125:37–44. PubMed PMC
Zhang Y, Moran AE. Trends in the prevalence, awareness, treatment, and control of hypertension among young adults in the United States, 1999 to 2014. Hypertension. 2017;70:736–742. PubMed PMC
Tziomalos K, Athyros VG, Karagiannis A, Mikhailidis DP. Dyslipidemia as a risk factor for ischemic stroke. Curr Top Med Chem. 2009;9:1291–1297. PubMed
Zhao L, Wang R, Song B, Tan S, Gao Y, Fang H, Lu J, Xu Y. Association between atherogenic dyslipidemia and recurrent stroke risk in patients with different subtypes of ischemic stroke. Int J Stroke. 2015;10:752–758. PubMed
Cook S, Kavey REW. Dyslipidemia and pediatric obesity. Pediatr Clin N Am. 2011;58:1363–1373. PubMed PMC
Kavey R-EW. Combined dyslipidemia in childhood. J Clin Lipidol. 2015;9:S41–S56. PubMed
Duarte AA, Mohsin S, Golubnitschaja O. Diabetes care in figures: current pitfalls and future scenario. EPMA J. 2018;9:125–131. PubMed PMC
Mayer-Davis EJ. Type 2 diabetes in youth: epidemiology and current research toward prevention and treatment. J Am Diet Assoc. 2008;108:S45–S51. PubMed
Pulgaron ER, Delamater AM. Obesity and type 2 diabetes in children: epidemiology and treatment. Curr Diab Rep. 2014;14:508. PubMed PMC
Kachur S, Lavie CJ, de Schutter A, Milani RV, Ventura HO. Obesity and cardiovascular diseases. Minerva Med. 2017;108:212–228. PubMed
Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration (BMI Mediated Effects) Lu Y, Hajifathalian K, Ezzati M, Woodward M, Rimm EB, et al. Metabolic mediators of the effects of body-mass index, overweight, and obesity on coronary heart disease and stroke: a pooled analysis of 97 prospective cohorts with 1·8 million participants. Lancet. 2014;383:970–983. PubMed PMC
Guo Y, Yue X-J, Li H-H, Song Z-X, Yan H-Q, Zhang P, Gui YK, Chang L, Li T. Overweight and obesity in young adulthood and the risk of stroke: a meta-analysis. J Stroke Cerebrovasc Dis. 2016;25:2995–3004. PubMed
Güngör NK. Overweight and obesity in children and adolescents. J Clin Res Pediatr Endocrinol. 2014;6:129–143. PubMed PMC
US Preventive Services Task Force. Grossman DC, Bibbins-Domingo K, Curry SJ, Barry MJ, Davidson KW, et al. Screening for Obesity in Children and Adolescents: US Preventive Services Task Force Recommendation Statement. JAMA. 2017;317:2417–2426. PubMed
Vine M, Hargreaves MB, Briefel RR, Orfield C. Expanding the role of primary care in the prevention and treatment of childhood obesity: a review of clinic- and community-based recommendations and interventions. J Obes. 2013;2013:172035. PubMed PMC
Bhaskaran K, Dos-Santos-Silva I, Leon DA, Douglas IJ, Smeeth L. Association of BMI with overall and cause-specific mortality: a population-based cohort study of 3·6 million adults in the UK. Lancet Diabetes Endocrinol. 2018;6:944–953. PubMed PMC
Shah RS, Cole JW. Smoking and stroke: the more you smoke the more you stroke. Expert Rev Cardiovasc Ther. 2010;8:917–932. PubMed PMC
Nordahl H, Osler M, Frederiksen BL, Andersen I, Prescott E, Overvad K, Diderichsen F, Rod NH. Combined effects of socioeconomic position, smoking, and hypertension on risk of ischemic and hemorrhagic stroke. Stroke. 2014;45:2582–2587. PubMed
Patra J, Taylor B, Irving H, Roerecke M, Baliunas D, Mohapatra S, Rehm J. Alcohol consumption and the risk of morbidity and mortality for different stroke types—a systematic review and meta-analysis. BMC Public Health. 2010;10:258. PubMed PMC
Reynolds K, Lewis B, Nolen JDL, Kinney GL, Sathya B, He J, et al. Alcohol consumption and risk of stroke: a meta-analysis. JAMA. 2003;289:579–588. PubMed
Kang B, Bae H-J. Moderate alcohol intake reduces risk of ischemic stroke in Korea. Neurology. 2016;86:1850. PubMed
Zhang C, Qin Y-Y, Chen Q, Jiang H, Chen X-Z, Xu C-L, Mao PJ, He J, Zhou YH. Alcohol intake and risk of stroke: a dose-response meta-analysis of prospective studies. Int J Cardiol. 2014;174:669–677. PubMed
Larsson SC, Wallin A, Wolk A, Markus HS. Differing association of alcohol consumption with different stroke types: a systematic review and meta-analysis. BMC Med. 2016;14:178. PubMed PMC
Puddey IB, Rakic V, Dimmitt SB, Beilin LJ. Influence of pattern of drinking on cardiovascular disease and cardiovascular risk factors—a review. Addiction. 1999;94:649–663. PubMed
Högström G, Nordström A, Eriksson M, Nordström P. Risk factors assessed in adolescence and the later risk of stroke in men: a 33-year follow-up study. Cerebrovasc Dis. 2015;39:63–71. PubMed
Patrick ME, Schulenberg JE, Martz ME, Maggs JL, O’Malley PM, Johnston LD. Extreme binge drinking among 12th-grade students in the United States: prevalence and predictors. JAMA Pediatr. 2013;167:1019–1025. PubMed PMC
Hall C, Heck JE, Sandler DP, Ritz B, Chen H, Krause N. Occupational and leisure-time physical activity differentially predict 6-year incidence of stroke and transient ischemic attack in women. Scand J Work Environ Health. 2018. PubMed PMC
Harari G, Green MS, Zelber-Sagi S. Combined association of occupational and leisure-time physical activity with all-cause and coronary heart disease mortality among a cohort of men followed-up for 22 years. Occup Environ Med. 2015;72:617–624. PubMed
Kim M-Y, Lee S, Myong YH, Lee YJ, Kim M-R, Shin J-S, Lee J, Ha IH. Association between sleep duration and stroke prevalence in Korean adults: a cross-sectional study. BMJ Open. 2018;8:e021491. PubMed PMC
He Q, Sun H, Wu X, Zhang P, Dai H, Ai C, Shi J. Sleep duration and risk of stroke: a dose-response meta-analysis of prospective cohort studies. Sleep Med. 2017;32:66–74. PubMed
Li W, Wang D, Cao S, Yin X, Gong Y, Gan Y, Zhou Y, Lu Z. Sleep duration and risk of stroke events and stroke mortality: a systematic review and meta-analysis of prospective cohort studies. Int J Cardiol. 2016;223:870–876. PubMed
Grandner MA, Jackson NJ, Pak VM, Gehrman PR. Sleep disturbance is associated with cardiovascular and metabolic disorders. J Sleep Res. 2012;21:427–433. PubMed PMC
Petrov ME, Howard G, Grandner MA, Kleindorfer D, Molano JR, Howard VJ. Sleep duration and risk of incident stroke by age, sex, and race: the REGARDS study. Neurology. 2018;91:e1702–e1709. PubMed PMC
Spengos K, Vemmos K. Risk factors, etiology, and outcome of first-ever ischemic stroke in young adults aged 15 to 45—the Athens young stroke registry. Eur J Neurol. 2010;17:1358–1364. PubMed
Banken JA. Drug abuse trends among youth in the United States. Ann N Y Acad Sci. 2004;1025:465–471. PubMed
Yang J, Zhang Y, Luo L, Meng R, Yu C. Global mortality burden of cirrhosis and liver cancer attributable to injection drug use, 1990-2016: an age-period-cohort and spatial autocorrelation analysis. Int J Environ Res Public Health. 2018:15. PubMed PMC
Hackam DG. Cannabis and stroke: systematic appraisal of case reports. Stroke. 2015;46:852–856. PubMed
Barber PA, Pridmore HM, Krishnamurthy V, Roberts S, Spriggs DA, Carter KN, Anderson NE. Cannabis, ischemic stroke, and transient ischemic attack: a case-control study. Stroke. 2013;44:2327–2329. PubMed
Hemachandra D, McKetin R, Cherbuin N, Anstey KJ. Heavy cannabis users at elevated risk of stroke: evidence from a general population survey. Aust N Z J Public Health. 2016;40:226–230. PubMed
Lappin JM, Darke S, Farrell M. Stroke and methamphetamine use in young adults: a review. J Neurol Neurosurg Psychiatry. 2017;88:1079–1091. PubMed
Yeung M, Bhalla A, Birns J. Recreational drug misuse and stroke. Curr Drug Abuse Rev. 2011;4:286–291. PubMed
Kurth T, Chabriat H, Bousser M-G. Migraine and stroke: a complex association with clinical implications. Lancet Neurol. 2012;11:92–100. PubMed
Schürks M, Rist PM, Bigal ME, Buring JE, Lipton RB, Kurth T. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ. 2009;339:b3914. PubMed PMC
Adelborg K, Szépligeti SK, Holland-Bill L, Ehrenstein V, Horváth-Puhó E, Henderson VW, et al. Migraine and risk of cardiovascular diseases: Danish population based matched cohort study. BMJ. 2018;360:k96. PubMed PMC
Tzourio C, Tehindrazanarivelo A, Iglésias S, Alpérovitch A, Chedru F, d’Anglejan-Chatillon J, et al. Case-control study of migraine and risk of ischaemic stroke in young women. BMJ. 1995;310:830–833. PubMed PMC
Tchaikovski SN, Rosing J. Mechanisms of estrogen-induced venous thromboembolism. Thromb Res. 2010;126:5–11. PubMed
Demel SL, Kittner S, Ley SH, McDermott M, Rexrode KM. Stroke risk factors unique to women. Stroke. 2018;49:518–523. PubMed PMC
Lidegaard Ø, Løkkegaard E, Jensen A, Skovlund CW, Keiding N. Thrombotic stroke and myocardial infarction with hormonal contraception. N Engl J Med. 2012;366:2257–2266. PubMed
Chakhtoura Z, Canonico M, Gompel A, Thalabard J-C, Scarabin P-Y, Plu-Bureau G. Progestogen-only contraceptives and the risk of stroke: a meta-analysis. Stroke. 2009;40:1059–1062. PubMed
Sells CM, Feske SK. Stroke in pregnancy. Semin Neurol. 2017;37:669–678. PubMed
Camargo EC, Feske SK, Singhal AB. Stroke in pregnancy: an update. Neurol Clin. 2019;37:131–148. PubMed
Bonamy A-KE, Parikh NI, Cnattingius S, Ludvigsson JF, Ingelsson E. Birth characteristics and subsequent risks of maternal cardiovascular disease: effects of gestational age and fetal growth. Circulation. 2011;124:2839–2846. PubMed
Bushnell C, McCullough LD, Awad IA, Chireau MV, Fedder WN, Furie KL, Howard VJ, Lichtman JH, Lisabeth LD, Piña IL, Reeves MJ, Rexrode KM, Saposnik G, Singh V, Towfighi A, Vaccarino V, Walters MR, American Heart Association Stroke Council. Council on Cardiovascular and Stroke Nursing. Council on Clinical Cardiology. Council on Epidemiology and Prevention. Council for High Blood Pressure Research Guidelines for the prevention of stroke in women: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:1545–1588. PubMed PMC
McDermott M, Miller EC, Rundek T, Hurn PD, Bushnell CD. Preeclampsia: association with posterior reversible encephalopathy syndrome and stroke. Stroke. 2018;49:524–530. PubMed PMC
Savitz DA, Danilack VA, Elston B, Lipkind HS. Pregnancy-induced hypertension and diabetes and the risk of cardiovascular disease, stroke, and diabetes hospitalization in the year following delivery. Am J Epidemiol. 2014;180:41–44. PubMed PMC
Konieczka K, Ritch R, Traverso CE, Kim DM, Kook MS, Gallino A, Golubnitschaja O, Erb C, Reitsamer HA, Kida T, Kurysheva N, Yao K. Flammer syndrome. EPMA J. 2014;5:11. PubMed PMC
Flammer Syndrome [Internet]. [cited 2018 Jul 12]. Available from: http://www.flammer-syndrome.ch/index.php?id=32
Flammer J, Konieczka K. The discovery of the Flammer syndrome: a historical and personal perspective. EPMA J. 2017;8:75–97. PubMed PMC
Konieczka K, Koch S, Binggeli T, Schoetzau A, Kesselring J. Multiple sclerosis and primary vascular dysregulation (Flammer syndrome) EPMA J. 2016;7:13. PubMed PMC
Smokovski I, Risteski M, Polivka J, Zubor P, Konieczka K, Costigliola V, Golubnitschaja O. Postmenopausal breast cancer: European challenge and innovative concepts. EPMA J. 2017;8:159–169. PubMed PMC
Zubor P, Gondova A, Polivka J, Kasajova P, Konieczka K, Danko J, Golubnitschaja O. Breast cancer and Flammer syndrome: any symptoms in common for prediction, prevention and personalised medical approach? EPMA J. 2017;8:129–140. PubMed PMC
Bubnov R, Polivka J, Zubor P, Konieczka K, Golubnitschaja O. “Pre-metastatic niches” in breast cancer: are they created by or prior to the tumour onset? “Flammer syndrome” relevance to address the question. EPMA J. 2017;8:141–157. PubMed PMC
Polivka J, Kralickova M, Polivka J, Kaiser C, Kuhn W, Golubnitschaja O. Mystery of the brain metastatic disease in breast cancer patients: improved patient stratification, disease prediction and targeted prevention on the horizon? EPMA J. 2017;8:119–127. PubMed PMC
Kunin A, Polivka J, Moiseeva N, Golubnitschaja O. “Dry mouth” and “Flammer” syndromes-neglected risks in adolescents and new concepts by predictive, preventive and personalised approach. EPMA J. 2018;9:307–317. PubMed PMC
Barthelmes J, Nägele MP, Ludovici V, Ruschitzka F, Sudano I, Flammer AJ. Endothelial dysfunction in cardiovascular disease and Flammer syndrome-similarities and differences. EPMA J. 2017;8:99–109. PubMed PMC
Gugleta K, Zawinka C, Rickenbacher I, Kochkorov A, Katamay R, Flammer J, Orgul S. Analysis of retinal vasodilation after flicker light stimulation in relation to vasospastic propensity. Invest Ophthalmol Vis Sci. 2006;47:4034–4041. PubMed
Donnelly J, Budohoski KP, Smielewski P, Czosnyka M. Regulation of the cerebral circulation: bedside assessment and clinical implications. Crit Care. 2016;20:129. PubMed PMC
Golubnitschaja O. Feeling cold and other underestimated symptoms in breast cancer: anecdotes or individual profiles for advanced patient stratification? EPMA J. 2017;8:17–22. PubMed PMC
Flammer J, Konieczka K, Flammer AJ. The primary vascular dysregulation syndrome: implications for eye diseases. EPMA J. 2013;4:14. PubMed PMC
Konieczka K, Erb C. Diseases potentially related to Flammer syndrome. EPMA J. 2017;8:327–332. PubMed PMC
Wesselink EM, Kappen TH, Torn HM, Slooter AJC, van Klei WA. Intraoperative hypotension and the risk of postoperative adverse outcomes: a systematic review. Br J Anaesth. 2018;121:706–721. PubMed
Golubnitschaja O, Flammer J. Individualised patient profile: clinical utility of Flammer syndrome phenotype and general lessons for predictive, preventive and personalised medicine. EPMA J. 2018;9:15–20. PubMed PMC
Allais G, Chiarle G, Sinigaglia S, Airola G, Schiapparelli P, Benedetto C. Estrogen, migraine, and vascular risk. Neurol Sci. 2018;39:11–20. PubMed
Fridman S, Sposato LA. Migraine with visual aura, incident AF, and stroke risk: is migraine with aura an embolic TIA? Neurology. 2018;91:1077–1078. PubMed
Sen S, Androulakis XM, Duda V, Alonso A, Chen LY, Soliman EZ, Magnani J, Trivedi T, Merchant AT, Gottesman RF, Rosamond WD. Migraine with visual aura is a risk factor for incident atrial fibrillation: a cohort study. Neurology. 2018;91:e2202–e2210. PubMed PMC
Sadrameli SS, Gadhia RR, Kabir R, Volpi JJ. Patent foramen Ovale in cryptogenic stroke and migraine with aura: does size matter? Cureus. 2018;10:e3213. PubMed PMC
Zhang DP, Li HR, Ma QK, Yin S, Peng YF, Zhang HL, Zhao M, Zhang SL. Prevalence of stroke and Hypoperfusion in patients with isolated vertigo and vascular risk factors. Front Neurol. 2018;9:974. PubMed PMC
Konieczka K, Ritch R, Traverso CE, Kim DM, Kook MS, Gallino A, Golubnitschaja O, Erb C, Reitsamer HA, Kida T, Kurysheva N, Yao K. Flammer syndrome. EPMA J. 2014;5:11. PubMed PMC
Huang Y-S, Koo M, Chen J-C, Hwang J-H. The association between tinnitus and the risk of ischemic cerebrovascular disease in young and middle-aged patients: a secondary case-control analysis of a nationwide, population-based health claims database. PLoS One. 2017;12:e0187474. PubMed PMC
Dehkharghani S, Fleischer CC, Qiu D, Yepes M, Tong F. Cerebral temperature dysregulation: MR thermographic monitoring in a nonhuman primate study of acute ischemic stroke. AJNR Am J Neuroradiol. 2017;38:712–720. PubMed PMC
Bahouth MN, Hillis A, Gottesman R. Abstract T MP86: a prospective study of the effect of dehydration on stroke severity and short term outcome. Stroke. 2015;46:ATMP86.
Yong WC, Sanguankeo A, Upala S. Association between primary Sjögren’s syndrome, cardiovascular and cerebrovascular disease: a systematic review and meta-analysis. Clin Exp Rheumatol. 2018;36(Suppl 112):190–197. PubMed
Yang D, Qiao L, Zhao LD. Cerebral infarction in a patient with primary Sjogren’s syndrome: a case report and literature review. Beijing Da Xue Xue Bao. 2016;48:1077–1080. PubMed
Baban B, Golubnitschaja O. The potential relationship between Flammer and Sjögren syndromes: the chime of dysfunction. EPMA J. 2017;8:333–338. PubMed PMC
Pache M, Kräuchi K, Cajochen C, Wirz-Justice A, Dubler B, Flammer J, Kaiser HJ. Cold feet and prolonged sleep-onset latency in vasospastic syndrome. Lancet. 2001;358:125–126. PubMed
Duss SB, Brill A-K, Bargiotas P, Facchin L, Alexiev F, Manconi M, Bassetti CL. Sleep-wake disorders in stroke-increased stroke risk and deteriorated recovery? An evaluation on the necessity for prevention and treatment. Curr Neurol Neurosci Rep. 2018;18:72. PubMed
Sabel BA, Wang J, Cárdenas-Morales L, Faiq M, Heim C. Mental stress as consequence and cause of vision loss: the dawn of psychosomatic ophthalmology for preventive and personalized medicine. EPMA J. 2018;9:133–160. PubMed PMC
Yeghiazaryan K, Flammer J, Golubnitschaja O. Predictive molecular profiling in blood of healthy vasospastic individuals: clue to targeted prevention as personalised medicine to effective costs. EPMA J. 2010;1:263–272. PubMed PMC
Golubnitschaja O, Yeghiazaryan K, Flammer J. Multiomic signature of glaucoma predisposition in Flammer syndrome affected individuals—innovative PPPM strategies in disease management. Flammer Syndrome and Associated Pathologies: Springer; 2019.
Handforth A, Parker GA. Conditions associated with essential tremor in veterans: a potential role for chronic stress. Tremor Other Hyperkinet Mov (N Y) 2018;8:517. PubMed PMC
Gowey MA, Khodneva Y, Tison SE, Carson AP, Cherrington AL, Howard VJ, et al. Depressive symptoms, perceived stress, and metabolic health: the REGARDS study. Int J Obes. 2018. 10.1038/s41366-018-0270-3. PubMed PMC
Anti-breast cancer effects of phytochemicals: primary, secondary, and tertiary care
Metabolic Anti-Cancer Effects of Melatonin: Clinically Relevant Prospects
Vaginal dryness: individualised patient profiles, risks and mitigating measures