Advertisement

EPMA Journal

, Volume 10, Issue 1, pp 81–99 | Cite as

Risks associated with the stroke predisposition at young age: facts and hypotheses in light of individualized predictive and preventive approach

  • Jiri PolivkaJr
  • Jiri Polivka
  • Martin Pesta
  • Vladimir Rohan
  • Libuse Celedova
  • Smit Mahajani
  • Ondrej Topolcan
  • Olga GolubnitschajaEmail author
Review

Abstract

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.

Keywords

Young adults Stroke Risk factors Individualized patient profile Etiology Vascular Abnormal BMI Blood flow Microcirculation Life style Sleep patterns Migraine Hormonal regulation Psychology Stress Screening program Flammer syndrome Phenotype Questionnaire Risk assessment Baroreceptor sensitivity Cardiac Circadian rhythm Tinnitus Thermoregulation Altered sensation Body dehydration Predictive preventive personalized medicine 

Notes

Authors’ contribution

OG is the project coordinator who has created the main scientific concepts presented in the manuscript. JP Jr., JP, and MP have performed the literature search, analyzed the data, and drafted the manuscript. SM has performed the literature search. VR, LC, and OT have contributed to the concepts’ development. OG and JP Jr. have designed the final version of the manuscript.

Funding information

This work was supported by the Charles University Research Fund (Progres Q39), by MH CZ-DRO (Faculty Hospital Plzen—FNPl, 00669806), and by the National Sustainability Program I (NPU I) Nr. LO1503 provided by the Ministry of Education Youth and Sports of the Czech Republic, and by the Grant of Czech Health Research Council No. 15-32727A. The authors thank the European Association for Predictive, Preventive and Personalized Medicine (EPMA, Brussels) for the professional support of the project.

Compliance with ethical standards

Not applicable.

Conflict of interest

The authors declare that they have no conflict of interest.

Statement of informed consent

Patients have not been involved in the study.

Statement of human and animal rights

No experiments have been performed including patients and/or animals.

References

  1. 1.
    Johnston SC, Mendis S, Mathers CD. Global variation in stroke burden and mortality: estimates from monitoring, surveillance, and modelling. Lancet Neurol. 2009;8:345–54.CrossRefPubMedGoogle Scholar
  2. 2.
    Béjot Y, Bailly H, Durier J, Giroud M. Epidemiology of stroke in Europe and trends for the 21st century. Presse Med. 2016;45:e391–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Polivka J, Polivka J, Rohan V. Predictive and individualized management of stroke—success story in Czech Republic. EPMA J. 2018 [cited 2018 Nov 26];9:393–401.  https://doi.org/10.1007/s13167-018-0150-x.CrossRefPubMedGoogle Scholar
  4. 4.
    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;10:315–25.CrossRefPubMedGoogle Scholar
  5. 5.
    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.Google Scholar
  6. 6.
    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;48:1744–51.CrossRefPubMedGoogle Scholar
  7. 7.
    von Sarnowski B, Putaala J, Grittner U, Gaertner B, Schminke U, Curtze S, et al. Lifestyle risk factors for ischemic stroke and transient ischemic attack in young adults in the stroke in young Fabry patients study. Stroke. 2013;44:119–25.CrossRefGoogle Scholar
  8. 8.
    Goeggel Simonetti B, Mono M-L, Huynh-Do U, Michel P, Odier C, Sztajzel R, et al. Risk factors, aetiology and outcome of ischaemic stroke in young adults: the Swiss young stroke study (SYSS). J Neurol. 2015;262:2025–32.CrossRefPubMedGoogle Scholar
  9. 9.
    Leung LY, Caplan LR. Factors associated with delay in presentation to the hospital for young adults with ischemic stroke. Cerebrovasc Dis. 2016;42:10–4.CrossRefPubMedGoogle Scholar
  10. 10.
    Polivka J, Krakorova K, Peterka M, Topolcan O. Current status of biomarker research in neurology. EPMA J. 2016;7:14.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Polívka J, Rohan V, Sevčík P, Polívka J. Personalized approach to primary and secondary prevention of ischemic stroke. EPMA J. 2014;5:9.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Tatlisumak T, Cucchiara B, Kuroda S, Kasner SE, Putaala J. Nontraumatic intracerebral haemorrhage in young adults. Nat Rev Neurol. 2018;14:237–50.CrossRefPubMedGoogle Scholar
  13. 13.
    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;70:51–7.CrossRefPubMedGoogle Scholar
  14. 14.
    Kwon SU, Kim JS, Lee JH, Lee MC. Ischemic stroke in Korean young adults. Acta Neurol Scand. 2000;101:19–24.CrossRefPubMedGoogle Scholar
  15. 15.
    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;43:3179–83.CrossRefPubMedGoogle Scholar
  16. 16.
    Yesilot Barlas N, Putaala J, Waje-Andreassen U, Vassilopoulou S, Nardi K, Odier C, et al. Etiology of first-ever ischaemic stroke in European young adults: the 15 cities young stroke study. Eur J Neurol. 2013;20:1431–9.PubMedGoogle Scholar
  17. 17.
    Mallick AA, Ganesan V, Kirkham FJ, Fallon P, Hedderly T, McShane T, et al. Childhood arterial ischaemic stroke incidence, presenting features, and risk factors: a prospective population-based study. Lancet Neurol. 2014;13:35–43.CrossRefPubMedGoogle Scholar
  18. 18.
    Gerstl L, Weinberger R, von Kries R, Heinen F, Schroeder AS, Bonfert MV, et al. Risk factors in childhood arterial ischaemic stroke: findings from a population-based study in Germany. Eur J Paediatr Neurol. 2018;22:380–6.CrossRefPubMedGoogle Scholar
  19. 19.
    Riel-Romero RMS, Kalra AA, Gonzalez-Toledo E. Childhood and teenage stroke. Neurol Res. 2009;31:775–84.CrossRefPubMedGoogle Scholar
  20. 20.
    Riel-Romero RMS. Neonatal stroke. Neurol Res. 2008;30:839–44.CrossRefPubMedGoogle Scholar
  21. 21.
    Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. 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.CrossRefPubMedGoogle Scholar
  22. 22.
    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.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Kissela BM, Khoury JC, Alwell K, Moomaw CJ, Woo D, Adeoye O, et al. Age at stroke: temporal trends in stroke incidence in a large, biracial population. Neurology. 2012;79:1781–7.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    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;70:713–21.CrossRefPubMedGoogle Scholar
  25. 25.
    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;85:509–13.CrossRefPubMedGoogle Scholar
  26. 26.
    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;35:1047–51.CrossRefPubMedGoogle Scholar
  27. 27.
    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.Google Scholar
  28. 28.
    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.Google Scholar
  29. 29.
    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;48:2925–30.CrossRefPubMedGoogle Scholar
  30. 30.
    Ning X, Sun J, Jiang R, Lu H, Bai L, Shi M, et al. Increased stroke burdens among the low-income young and middle aged in rural China. Stroke. 2017;48:77–83.CrossRefPubMedGoogle Scholar
  31. 31.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Sarfo FS, Ovbiagele B, Gebregziabher M, Wahab K, Akinyemi R, Akpalu A, et al. Stroke among young west Africans: evidence from the SIREN (stroke investigative research and educational network) large multisite case-control study. Stroke. 2018;49:1116–22.CrossRefPubMedGoogle Scholar
  33. 33.
    Ferro JM, Massaro AR, Mas J-L. Aetiological diagnosis of ischaemic stroke in young adults. Lancet Neurol. 2010;9:1085–96.CrossRefPubMedGoogle Scholar
  34. 34.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    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;27:1047–53.CrossRefPubMedGoogle Scholar
  36. 36.
    Wijnhoven TMA, van Raaij JMA, Spinelli A, Rito AI, Hovengen R, Kunesova M, et al. 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.CrossRefPubMedGoogle Scholar
  37. 37.
    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;388:761–75.CrossRefPubMedGoogle Scholar
  38. 38.
    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.CrossRefPubMedGoogle Scholar
  39. 39.
    Jood K, Ladenvall P, Tjärnlund-Wolf A, Ladenvall C, Andersson M, Nilsson S, et al. Fibrinolytic gene polymorphism and ischemic stroke. Stroke. 2005;36:2077–81.CrossRefPubMedGoogle Scholar
  40. 40.
    Bevan S, Traylor M, Adib-Samii P, Malik R, Paul NLM, Jackson C, et al. Genetic heritability of ischemic stroke and the contribution of previously reported candidate gene and genomewide associations. Stroke. 2012;43:3161–7.CrossRefPubMedGoogle Scholar
  41. 41.
    Falcone GJ, Malik R, Dichgans M, Rosand J. Current concepts and clinical applications of stroke genetics. Lancet Neurol. 2014;13:405–18.CrossRefPubMedGoogle Scholar
  42. 42.
    Chauhan G, Debette S. Genetic risk factors for ischemic and hemorrhagic stroke. Curr Cardiol Rep. 2016;18:124.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    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;53:2182–4.CrossRefPubMedGoogle Scholar
  44. 44.
    Goto Y, Horai S, Matsuoka T, Koga Y, Nihei K, Kobayashi M, et al. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS): a correlative study of the clinical features and mitochondrial DNA mutation. Neurology. 1992;42:545–50.CrossRefPubMedGoogle Scholar
  45. 45.
    Kaufmann P, Engelstad K, Wei Y, Kulikova R, Oskoui M, Battista V, et al. Protean phenotypic features of the A3243G mitochondrial DNA mutation. Arch Neurol. 2009;66:85–91.CrossRefPubMedGoogle Scholar
  46. 46.
    Sharma P, Yadav S, Meschia JF. Genetics of ischaemic stroke. J Neurol Neurosurg Psychiatry. 2013;84:1302–8.CrossRefPubMedGoogle Scholar
  47. 47.
    Razvi SSM, Bone I. Single gene disorders causing ischaemic stroke. J Neurol. 2006;253:685–700.CrossRefPubMedGoogle Scholar
  48. 48.
    Chabriat H, Joutel A, Dichgans M, Tournier-Lasserve E, Bousser M-G. Cadasil. Lancet Neurol. 2009;8:643–53.CrossRefPubMedGoogle Scholar
  49. 49.
    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.CrossRefPubMedGoogle Scholar
  50. 50.
    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.Google Scholar
  51. 51.
    Germain DP. Fabry disease. Orphanet J Rare Dis. 2010;5:30.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Zarate YA, Hopkin RJ. Fabry’s disease. Lancet. 2008;372:1427–35.CrossRefPubMedGoogle Scholar
  53. 53.
    Toyooka K. Fabry disease. Curr Opin Neurol. 2011;24:463–8.CrossRefPubMedGoogle Scholar
  54. 54.
    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;125:205–16.CrossRefPubMedGoogle Scholar
  55. 55.
    Wald NJ, Law M, Haddow JE, Craig WY. Apolipoprotiens and prediction of fatal myocardial infarction. Lancet. 2002;359:1864.CrossRefPubMedGoogle Scholar
  56. 56.
    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;12:40–4.CrossRefPubMedGoogle Scholar
  57. 57.
    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;39:7957–63.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Guo J, Liu A, Su D. Genetics of stroke. Acta Pharmacol Sin. 2010;31:1055–64.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    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;61:1652–61.CrossRefPubMedGoogle Scholar
  60. 60.
    Bersano A, Ballabio E, Bresolin N, Candelise L. Genetic polymorphisms for the study of multifactorial stroke. Hum Mutat. 2008;29:776–95.CrossRefPubMedGoogle Scholar
  61. 61.
    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;47:217–22.CrossRefPubMedGoogle Scholar
  62. 62.
    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;41:1599–603.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Ibrahim-Verbaas CA, Fornage M, Bis JC, Choi SH, Psaty BM, Meigs JB, et al. Predicting stroke through genetic risk functions: the CHARGE risk score project. Stroke. 2014;45:403–12.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Gudbjartsson DF, Arnar DO, Helgadottir A, Gretarsdottir S, Holm H, Sigurdsson A, et al. Variants conferring risk of atrial fibrillation on chromosome 4q25. Nature. 2007;448:353–7.CrossRefPubMedGoogle Scholar
  65. 65.
    Lemmens R, Buysschaert I, Geelen V, Fernandez-Cadenas I, Montaner J, Schmidt H, et al. The association of the 4q25 susceptibility variant for atrial fibrillation with stroke is limited to stroke of cardioembolic etiology. Stroke. 2010;41:1850–7.CrossRefPubMedGoogle Scholar
  66. 66.
    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;44:328–33.CrossRefGoogle Scholar
  67. 67.
    Traylor M, Farrall M, Holliday EG, Sudlow C, Hopewell JC, Cheng Y-C, et al. Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration): a meta-analysis of genome-wide association studies. Lancet Neurol. 2012;11:951–62.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Ikram MA, Seshadri S, Bis JC, Fornage M, DeStefano AL, Aulchenko YS, et al. Genomewide association studies of stroke. N Engl J Med. 2009;360:1718–28.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Traylor M, Mäkelä K-M, Kilarski LL, Holliday EG, Devan WJ, Nalls MA, et al. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Rutten-Jacobs LCA, Maaijwee NAM, Arntz RM, Schoonderwaldt HC, Dorresteijn LD, van der Vlugt MJ, et al. Long-term risk of recurrent vascular events after young stroke: the FUTURE study. Ann Neurol. 2013;74:592–601.CrossRefPubMedGoogle Scholar
  71. 71.
    Putaala J, Haapaniemi E, Kaste M, Tatlisumak T. How does number of risk factors affect prognosis in young patients with ischemic stroke? Stroke. 2012;43:356–61.CrossRefPubMedGoogle Scholar
  72. 72.
    Li F, Yang L, Yang R, Xu W, Chen F-P, Li N, et al. Ischemic stroke in young adults of northern China: characteristics and risk factors for recurrence. Eur Neurol. 2017;77:115–22.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Renna R, Pilato F, Profice P, Della Marca G, Broccolini A, Morosetti R, et al. Risk factor and etiology analysis of ischemic stroke in young adult patients. J Stroke Cerebrovasc Dis. 2014;23:e221–7.CrossRefPubMedGoogle Scholar
  74. 74.
    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;22:61–3.CrossRefPubMedGoogle Scholar
  75. 75.
    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;46:1690–2.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    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.CrossRefGoogle Scholar
  77. 77.
    Cui R, Iso H, Toyoshima H, Date C, Yamamoto A, Kikuchi S, et al. Body mass index and mortality from cardiovascular disease among Japanese men and women: the JACC study. Stroke. 2005;36:1377–82.CrossRefPubMedGoogle Scholar
  78. 78.
    Markidan J, Cole JW, Cronin CA, Merino JG, Phipps MS, Wozniak MA, et al. Smoking and risk of ischemic stroke in young men. Stroke. 2018;49:1276–8.CrossRefPubMedGoogle Scholar
  79. 79.
    Bhat VM, Cole JW, Sorkin JD, Wozniak MA, Malarcher AM, Giles WH, et al. Dose-response relationship between cigarette smoking and risk of ischemic stroke in young women. Stroke. 2008;39:2439–43.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    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;21:441–7.CrossRefPubMedGoogle Scholar
  81. 81.
    Sloan MA, Kittner SJ, Feeser BR, Gardner J, Epstein A, Wozniak MA, et al. Illicit drug-associated ischemic stroke in the Baltimore-Washington young stroke study. Neurology. 1998;50:1688–93.CrossRefPubMedGoogle Scholar
  82. 82.
    Wolff V, Lauer V, Rouyer O, Sellal F, Meyer N, Raul JS, et al. Cannabis use, ischemic stroke, and multifocal intracranial vasoconstriction: a prospective study in 48 consecutive young patients. Stroke. 2011;42:1778–80.CrossRefPubMedGoogle Scholar
  83. 83.
    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.CrossRefPubMedGoogle Scholar
  84. 84.
    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.Google Scholar
  85. 85.
    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.CrossRefPubMedGoogle Scholar
  86. 86.
    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.Google Scholar
  87. 87.
    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;174:302–9.CrossRefPubMedGoogle Scholar
  88. 88.
    González-Gómez FJ, Pérez-Torre P, DeFelipe A, Vera R, Matute C, Cruz-Culebras A, et al. Stroke in young adults: incidence rate, risk factors, treatment and prognosis. Rev Clin Esp. 2016;216:345–51.CrossRefPubMedGoogle Scholar
  89. 89.
    Lightbody CE, Clegg A, Patel K, Lucas JC, Storey H, Hackett ML, et al. Systematic review and meta-analysis of psychosocial risk factors for stroke. Semin Neurol. 2017;37:294–306.CrossRefPubMedGoogle Scholar
  90. 90.
    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.CrossRefPubMedGoogle Scholar
  91. 91.
    Seshadri S, Beiser A, Kelly-Hayes M, Kase CS, Au R, Kannel WB, et al. The lifetime risk of stroke: estimates from the Framingham study. Stroke. 2006;37:345–50.CrossRefPubMedGoogle Scholar
  92. 92.
    Turin TC, Okamura T, Afzal AR, Rumana N, Watanabe M, Higashiyama A, et al. Hypertension and lifetime risk of stroke. J Hypertens. 2016;34:116–22.CrossRefPubMedGoogle Scholar
  93. 93.
    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.CrossRefPubMedGoogle Scholar
  94. 94.
    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;70:736–42.CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Tziomalos K, Athyros VG, Karagiannis A, Mikhailidis DP. Dyslipidemia as a risk factor for ischemic stroke. Curr Top Med Chem. 2009;9:1291–7.CrossRefPubMedGoogle Scholar
  96. 96.
    Zhao L, Wang R, Song B, Tan S, Gao Y, Fang H, et al. Association between atherogenic dyslipidemia and recurrent stroke risk in patients with different subtypes of ischemic stroke. Int J Stroke. 2015;10:752–8.CrossRefPubMedGoogle Scholar
  97. 97.
    Cook S, Kavey REW. Dyslipidemia and pediatric obesity. Pediatr Clin N Am. 2011;58:1363–73 ix.CrossRefGoogle Scholar
  98. 98.
    Kavey R-EW. Combined dyslipidemia in childhood. J Clin Lipidol. 2015;9:S41–56.CrossRefPubMedGoogle Scholar
  99. 99.
    Duarte AA, Mohsin S, Golubnitschaja O. Diabetes care in figures: current pitfalls and future scenario. EPMA J. 2018;9:125–31.CrossRefPubMedGoogle Scholar
  100. 100.
    Mayer-Davis EJ. Type 2 diabetes in youth: epidemiology and current research toward prevention and treatment. J Am Diet Assoc. 2008;108:S45–51.CrossRefPubMedGoogle Scholar
  101. 101.
    Pulgaron ER, Delamater AM. Obesity and type 2 diabetes in children: epidemiology and treatment. Curr Diab Rep. 2014;14:508.CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Kachur S, Lavie CJ, de Schutter A, Milani RV, Ventura HO. Obesity and cardiovascular diseases. Minerva Med. 2017;108:212–28.PubMedGoogle Scholar
  103. 103.
    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;383:970–83.CrossRefGoogle Scholar
  104. 104.
    Guo Y, Yue X-J, Li H-H, Song Z-X, Yan H-Q, Zhang P, et al. Overweight and obesity in young adulthood and the risk of stroke: a meta-analysis. J Stroke Cerebrovasc Dis. 2016;25:2995–3004.CrossRefPubMedGoogle Scholar
  105. 105.
    Güngör NK. Overweight and obesity in children and adolescents. J Clin Res Pediatr Endocrinol. 2014;6:129–43.CrossRefPubMedGoogle Scholar
  106. 106.
    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;317:2417–26.CrossRefGoogle Scholar
  107. 107.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108.
    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;6:944–53.CrossRefPubMedPubMedCentralGoogle Scholar
  109. 109.
    Shah RS, Cole JW. Smoking and stroke: the more you smoke the more you stroke. Expert Rev Cardiovasc Ther. 2010;8:917–32.CrossRefPubMedPubMedCentralGoogle Scholar
  110. 110.
    Nordahl H, Osler M, Frederiksen BL, Andersen I, Prescott E, Overvad K, et al. Combined effects of socioeconomic position, smoking, and hypertension on risk of ischemic and hemorrhagic stroke. Stroke. 2014;45:2582–7.CrossRefPubMedGoogle Scholar
  111. 111.
    Patra J, Taylor B, Irving H, Roerecke M, Baliunas D, Mohapatra S, et al. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  112. 112.
    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;289:579–88.CrossRefPubMedGoogle Scholar
  113. 113.
    Kang B, Bae H-J. Moderate alcohol intake reduces risk of ischemic stroke in Korea. Neurology. 2016;86:1850.CrossRefPubMedGoogle Scholar
  114. 114.
    Zhang C, Qin Y-Y, Chen Q, Jiang H, Chen X-Z, Xu C-L, et al. Alcohol intake and risk of stroke: a dose-response meta-analysis of prospective studies. Int J Cardiol. 2014;174:669–77.CrossRefPubMedGoogle Scholar
  115. 115.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  116. 116.
    Puddey IB, Rakic V, Dimmitt SB, Beilin LJ. Influence of pattern of drinking on cardiovascular disease and cardiovascular risk factors—a review. Addiction. 1999;94:649–63.CrossRefPubMedGoogle Scholar
  117. 117.
    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.CrossRefPubMedGoogle Scholar
  118. 118.
    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;167:1019–25.CrossRefPubMedGoogle Scholar
  119. 119.
    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.Google Scholar
  120. 120.
    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;72:617–24.CrossRefPubMedGoogle Scholar
  121. 121.
    Kim M-Y, Lee S, Myong YH, Lee YJ, Kim M-R, Shin J-S, et al. Association between sleep duration and stroke prevalence in Korean adults: a cross-sectional study. BMJ Open. 2018;8:e021491.CrossRefPubMedPubMedCentralGoogle Scholar
  122. 122.
    He Q, Sun H, Wu X, Zhang P, Dai H, Ai C, et al. Sleep duration and risk of stroke: a dose-response meta-analysis of prospective cohort studies. Sleep Med. 2017;32:66–74.CrossRefPubMedGoogle Scholar
  123. 123.
    Li W, Wang D, Cao S, Yin X, Gong Y, Gan Y, et al. Sleep duration and risk of stroke events and stroke mortality: a systematic review and meta-analysis of prospective cohort studies. Int J Cardiol. 2016;223:870–6.CrossRefPubMedGoogle Scholar
  124. 124.
    Grandner MA, Jackson NJ, Pak VM, Gehrman PR. Sleep disturbance is associated with cardiovascular and metabolic disorders. J Sleep Res. 2012;21:427–33.CrossRefPubMedGoogle Scholar
  125. 125.
    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:e1702–9.CrossRefPubMedGoogle Scholar
  126. 126.
    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;17:1358–64.CrossRefPubMedGoogle Scholar
  127. 127.
    Banken JA. Drug abuse trends among youth in the United States. Ann N Y Acad Sci. 2004;1025:465–71.CrossRefPubMedGoogle Scholar
  128. 128.
    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.Google Scholar
  129. 129.
    Hackam DG. Cannabis and stroke: systematic appraisal of case reports. Stroke. 2015;46:852–6.CrossRefPubMedGoogle Scholar
  130. 130.
    Barber PA, Pridmore HM, Krishnamurthy V, Roberts S, Spriggs DA, Carter KN, et al. Cannabis, ischemic stroke, and transient ischemic attack: a case-control study. Stroke. 2013;44:2327–9.CrossRefPubMedGoogle Scholar
  131. 131.
    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;40:226–30.CrossRefPubMedGoogle Scholar
  132. 132.
    Lappin JM, Darke S, Farrell M. Stroke and methamphetamine use in young adults: a review. J Neurol Neurosurg Psychiatry. 2017;88:1079–91.CrossRefPubMedGoogle Scholar
  133. 133.
    Yeung M, Bhalla A, Birns J. Recreational drug misuse and stroke. Curr Drug Abuse Rev. 2011;4:286–91.CrossRefPubMedGoogle Scholar
  134. 134.
    Kurth T, Chabriat H, Bousser M-G. Migraine and stroke: a complex association with clinical implications. Lancet Neurol. 2012;11:92–100.CrossRefPubMedGoogle Scholar
  135. 135.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  136. 136.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  137. 137.
    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;310:830–3.CrossRefPubMedPubMedCentralGoogle Scholar
  138. 138.
    Tchaikovski SN, Rosing J. Mechanisms of estrogen-induced venous thromboembolism. Thromb Res. 2010;126:5–11.CrossRefPubMedGoogle Scholar
  139. 139.
    Demel SL, Kittner S, Ley SH, McDermott M, Rexrode KM. Stroke risk factors unique to women. Stroke. 2018;49:518–23.CrossRefPubMedPubMedCentralGoogle Scholar
  140. 140.
    Lidegaard Ø, Løkkegaard E, Jensen A, Skovlund CW, Keiding N. Thrombotic stroke and myocardial infarction with hormonal contraception. N Engl J Med. 2012;366:2257–66.CrossRefPubMedGoogle Scholar
  141. 141.
    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;40:1059–62.CrossRefPubMedGoogle Scholar
  142. 142.
    Sells CM, Feske SK. Stroke in pregnancy. Semin Neurol. 2017;37:669–78.CrossRefPubMedGoogle Scholar
  143. 143.
    Camargo EC, Feske SK, Singhal AB. Stroke in pregnancy: an update. Neurol Clin. 2019;37:131–48.CrossRefPubMedGoogle Scholar
  144. 144.
    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;124:2839–46.CrossRefPubMedGoogle Scholar
  145. 145.
    Bushnell C, McCullough LD, Awad IA, Chireau MV, Fedder WN, Furie KL, et al. Guidelines for the prevention of stroke in women: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:1545–88.CrossRefPubMedGoogle Scholar
  146. 146.
    McDermott M, Miller EC, Rundek T, Hurn PD, Bushnell CD. Preeclampsia: association with posterior reversible encephalopathy syndrome and stroke. Stroke. 2018;49:524–30.CrossRefPubMedPubMedCentralGoogle Scholar
  147. 147.
    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;180:41–4.CrossRefPubMedPubMedCentralGoogle Scholar
  148. 148.
    Konieczka K, Ritch R, Traverso CE, Kim DM, Kook MS, Gallino A, et al. Flammer syndrome. EPMA J. 2014;5:11.CrossRefPubMedPubMedCentralGoogle Scholar
  149. 149.
    Flammer Syndrome [Internet]. [cited 2018 Jul 12]. Available from: http://www.flammer-syndrome.ch/index.php?id=32
  150. 150.
    Flammer J, Konieczka K. The discovery of the Flammer syndrome: a historical and personal perspective. EPMA J. 2017;8:75–97.CrossRefPubMedPubMedCentralGoogle Scholar
  151. 151.
    Konieczka K, Koch S, Binggeli T, Schoetzau A, Kesselring J. Multiple sclerosis and primary vascular dysregulation (Flammer syndrome). EPMA J. 2016;7:13.CrossRefPubMedPubMedCentralGoogle Scholar
  152. 152.
    Smokovski I, Risteski M, Polivka J, Zubor P, Konieczka K, Costigliola V, et al. Postmenopausal breast cancer: European challenge and innovative concepts. EPMA J. 2017;8:159–69.CrossRefPubMedPubMedCentralGoogle Scholar
  153. 153.
    Zubor P, Gondova A, Polivka J, Kasajova P, Konieczka K, Danko J, et al. Breast cancer and Flammer syndrome: any symptoms in common for prediction, prevention and personalised medical approach? EPMA J. 2017;8:129–40.CrossRefPubMedPubMedCentralGoogle Scholar
  154. 154.
    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;8:141–57.CrossRefPubMedPubMedCentralGoogle Scholar
  155. 155.
    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;8:119–27.CrossRefPubMedPubMedCentralGoogle Scholar
  156. 156.
    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;9:307–17.CrossRefPubMedGoogle Scholar
  157. 157.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  158. 158.
    Gugleta K, Zawinka C, Rickenbacher I, Kochkorov A, Katamay R, Flammer J, et al. Analysis of retinal vasodilation after flicker light stimulation in relation to vasospastic propensity. Invest Ophthalmol Vis Sci. 2006;47:4034–41.CrossRefPubMedGoogle Scholar
  159. 159.
    Donnelly J, Budohoski KP, Smielewski P, Czosnyka M. Regulation of the cerebral circulation: bedside assessment and clinical implications. Crit Care. 2016;20:129.CrossRefPubMedPubMedCentralGoogle Scholar
  160. 160.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  161. 161.
    Flammer J, Konieczka K, Flammer AJ. The primary vascular dysregulation syndrome: implications for eye diseases. EPMA J. 2013;4:14.CrossRefPubMedPubMedCentralGoogle Scholar
  162. 162.
    Konieczka K, Erb C. Diseases potentially related to Flammer syndrome. EPMA J. 2017;8:327–32.CrossRefPubMedPubMedCentralGoogle Scholar
  163. 163.
    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;121:706–21.CrossRefPubMedGoogle Scholar
  164. 164.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  165. 165.
    Allais G, Chiarle G, Sinigaglia S, Airola G, Schiapparelli P, Benedetto C. Estrogen, migraine, and vascular risk. Neurol Sci. 2018;39:11–20.CrossRefPubMedGoogle Scholar
  166. 166.
    Fridman S, Sposato LA. Migraine with visual aura, incident AF, and stroke risk: is migraine with aura an embolic TIA? Neurology. 2018;91:1077–8.CrossRefPubMedGoogle Scholar
  167. 167.
    Sen S, Androulakis XM, Duda V, Alonso A, Chen LY, Soliman EZ, et al. Migraine with visual aura is a risk factor for incident atrial fibrillation: a cohort study. Neurology. 2018;91:e2202–10.CrossRefPubMedPubMedCentralGoogle Scholar
  168. 168.
    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.PubMedPubMedCentralGoogle Scholar
  169. 169.
    Zhang DP, Li HR, Ma QK, Yin S, Peng YF, Zhang HL, et al. Prevalence of stroke and Hypoperfusion in patients with isolated vertigo and vascular risk factors. Front Neurol. 2018;9:974.CrossRefPubMedPubMedCentralGoogle Scholar
  170. 170.
    Konieczka K, Ritch R, Traverso CE, Kim DM, Kook MS, Gallino A, et al. Flammer syndrome. EPMA J. 2014;5:11.CrossRefPubMedPubMedCentralGoogle Scholar
  171. 171.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  172. 172.
    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;38:712–20.CrossRefPubMedPubMedCentralGoogle Scholar
  173. 173.
    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.Google Scholar
  174. 174.
    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):190–7.PubMedGoogle Scholar
  175. 175.
    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;48:1077–80.PubMedGoogle Scholar
  176. 176.
    Baban B, Golubnitschaja O. The potential relationship between Flammer and Sjögren syndromes: the chime of dysfunction. EPMA J. 2017;8:333–8.CrossRefPubMedPubMedCentralGoogle Scholar
  177. 177.
    Pache M, Kräuchi K, Cajochen C, Wirz-Justice A, Dubler B, Flammer J, et al. Cold feet and prolonged sleep-onset latency in vasospastic syndrome. Lancet. 2001;358:125–6.CrossRefPubMedGoogle Scholar
  178. 178.
    Duss SB, Brill A-K, Bargiotas P, Facchin L, Alexiev F, Manconi M, et al. 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.CrossRefPubMedGoogle Scholar
  179. 179.
    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;9:133–60.CrossRefPubMedGoogle Scholar
  180. 180.
    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;1:263–72.CrossRefPubMedPubMedCentralGoogle Scholar
  181. 181.
    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.Google Scholar
  182. 182.
    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.Google Scholar
  183. 183.
    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.  https://doi.org/10.1038/s41366-018-0270-3.

Copyright information

© European Association for Predictive, Preventive and Personalised Medicine (EPMA) 2019

Authors and Affiliations

  • Jiri PolivkaJr
    • 1
    • 2
    • 3
  • Jiri Polivka
    • 3
  • Martin Pesta
    • 2
    • 4
  • Vladimir Rohan
    • 3
  • Libuse Celedova
    • 5
  • Smit Mahajani
    • 6
  • Ondrej Topolcan
    • 7
  • Olga Golubnitschaja
    • 8
    • 9
    • 10
    Email author
  1. 1.Department of Histology and Embryology, Faculty of Medicine in PilsenCharles UniversityStaré MěstoCzech Republic
  2. 2.Biomedical Centre, Faculty of Medicine in PilsenCharles UniversityStaré MěstoCzech Republic
  3. 3.Department of Neurology, University Hospital Pilsen, and Faculty of Medicine in PilsenCharles UniversityStaré MěstoCzech Republic
  4. 4.Department of Biology, Faculty of Medicine in PilsenCharles UniversityStaré MěstoCzech Republic
  5. 5.Department of Social and Assessment Medicine, Faculty of Medicine in PilsenCharles UniversityStaré MěstoCzech Republic
  6. 6.CEMBIO, University of BonnBonnGermany
  7. 7.Department of ImmunochemistryUniversity Hospital PilsenPilsenCzech Republic
  8. 8.Radiological Clinic, UKBRheinische Friedrich-Wilhelms-Universität BonnBonnGermany
  9. 9.Breast Cancer Research Centre, UKBRheinische Friedrich-Wilhelms-Universität BonnBonnGermany
  10. 10.Centre for Integrated Oncology, Cologne-Bonn, UKBRheinische Friedrich-Wilhelms-Universität BonnBonnGermany

Personalised recommendations