Determinants of premature familial arterial thrombosis in patients with juvenile ischaemic stroke

 

 Buy Article Permissions and Reprints

Summary

Factors predicting family history (FH) of premature arterial thrombosis in young patients with ischaemic stroke (IS) have not been extensively investigated, and whether they might influence the risk of post-stroke recurrence is still unknown. In the present study we analysed 1,881 consecutive first-ever IS patients aged 18–45 years recruited from January 2000 to January 2012 as part of the Italian Project on Stroke in Young Adults (IPSYS). FH of premature arterial thrombosis was any thrombotic event [IS, myocardial infarction or other arterial events event] > 45 years in proband’s first-degree relatives. Compared with patients without FH of premature arterial thrombosis, those with FH (n= 85) were more often smokers (odds ratio [OR], 1.94; 95 % confidence interval [CI], 1.21–3.09) and carriers of procoagulant abnormalities (OR, 3.66; 95 % CI, 2.21–6.06). Smoking (OR, 2.48; 95 % CI, 1.20–5.15), the A1691 mutation in factor V gene (OR, 3.64; 95 % CI, 1.31–10.10), and the A20210 mutation in the prothrombin gene (OR, 8.40; 95 % CI 3.35–21.05) were associated with FH of premature stroke (n = 33), while circulating anti-phospholipids to FH of premature myocardial infarction (n = 45; OR, 3.48; 95 % CI, 1.61–7.51). Mean follow-up time was 46.6 ± 38.6 months. Recurrent events occurred more frequently in the subgroup of patients with FH of premature stroke [19.4 %); p = 0.051] compared to patients without such a FH. In conclusion, young IS patients with FH of premature arterial thrombosis exhibit a distinct risk-factor profile, an underlying procoagulant state and have worse vascular prognosis than those with no FH of juvenile thrombotic events.

• References

• 1 Flossmann E, Schulz UGR, Rothwell PM. Systematic review of methods and results of studies of the genetic epidemiology of ischaemic stroke. Stroke 2004; 35: 212-227.
  CrossrefPubMedGoogle Scholar
• 2 Seshadri S, Beiser A, Pikula A. et al. Parental occurrence of stroke and risk of stroke in their children: the Framingham study. Circulation 2010; 121: 1304-1312.
  CrossrefPubMedGoogle Scholar
• 3 Jerrard-Dunne P, Cloud G, Hassan A. et al. Evaluating the genetic component of ischaemic stroke subtypes: a family history study. Stroke 2003; 34: 1364-1369.
  CrossrefPubMedGoogle Scholar
• 4 Jood K, Ladenvall C, Rosengren A. et al. Family history in ischaemic stroke before 70 years of age: the Sahlgrenska Academy Study on Ischaemic Stroke. Stroke 2005; 36: 1383-1387.
  CrossrefPubMedGoogle Scholar
• 5 Schulz UG, Flossmann E, Rothwell PM. Heritability of ischaemic stroke in relation to age, vascular risk factors, and subtypes of incident stroke in population-based studies. Stroke 2004; 35: 819-824.
  CrossrefPubMedGoogle Scholar
• 6 Flossmann E, Schulz UG, Rothwell PM. Potential confounding by intermediate phenotypes in studies of the genetics of ischaemic stroke. Cerebrovasc Dis 2005; 19: 1-10.
  CrossrefPubMedGoogle Scholar
• 7 Meschia JF, Atkinson EJ, O’Brien PC. et al. Familial clustering of stroke according to proband age at onset of presenting ischaemic stroke. Stroke 2003; 34: e89-e91.
  CrossrefPubMedGoogle Scholar
• 8 Kim RJ, Becker RC. Association between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations and events of the arterial circulatory system: a meta-analysis of published studies. Heart J 2003; 146: 948-957.
  CrossrefPubMedGoogle Scholar
• 9 Casas JP, Hingorani AD, Bautista LE, Sharma P. Meta-analysis of genetic studies in ischaemic stroke: thirty-two genes involving approximately 18, 000 cases and 58, 000 controls. Arch Neurol 2004; 61: 1652-1661.
  CrossrefPubMedGoogle Scholar
• 10 Pezzini A, Grassi M, Lodigiani C. et al. Predictors of migraine subtypes in young adults with ischaemic stroke. The Italian Project on Stroke in Young Adults (IPSYS). Stroke 2011; 42: 17-21.
  CrossrefPubMedGoogle Scholar
• 11 Pezzini A, Grassi M, Lodigiani C. et al. Predictors of Long-Term Recurrent Vascular Events after Ischaemic Stroke at Young Age: The Italian Project on Stroke in Young Adults. Circulation 2014; 129: 1668-1676.
  CrossrefPubMedGoogle Scholar
• 12 European Stroke Initiative: European Stroke Initiative recommendations for stroke management. European Stroke Council, European Neurological Society and European Federation of Neurological Societies. Cerebrovasc Dis 2000; 10: 335-351.
  CrossrefPubMedGoogle Scholar
• 13 Ripoll L, Paulin D, Drouet LO. Multiplex PCR-mediated site-directed mutagen-esis for one-step determination of Factor V Leiden and G20210A transition of the Prothrombin gene. Thromb Haemost 1997; 78: 960-961.
  Article in Thieme ConnectPubMedGoogle Scholar
• 14 Lee DS, Pencina MJ, Benjamin EJ. et al. Association of parental heart failure with risk of heart failure in offspring. N Engl J Med 2006; 355: 138-147.
  CrossrefPubMedGoogle Scholar
• 15 Touze’ E, Rothwell PM. Heritability of ischaemic stroke in women compared with men: a genetic epidemiological study. Lancet Neurol 2007; 6: 125-133.
  CrossrefPubMedGoogle Scholar
• 16 Siegerink B, Govers-Riemslag JWP, Rosendaal FR. et al. Intrinsic coagulation activation and the risk of arterial thrombosis in young women. Results from the Risk of Arterial Thrombosis in Relation to Oral Contraceptives (RATIO) case-control study. Circulation 2010; 122: 1854-1861.
  CrossrefPubMedGoogle Scholar
• 17 Urbanus RT, Siegerink B, Roest M. et al. Antiphospholipid antibodies and risk of myocardial infarction and ischaemic stroke in young women in the RATIO study: a case-control study. Lancet Neurol 2009; 8: 998-1005.
  CrossrefPubMedGoogle Scholar
• 18 Mulders TA, Meyer Z, van der Donk C. et al. Patients with premature cardiovascular disease and a positive family history for cardiovascular disease are prone to recurrent events. Int J Cardiol 2011; 153: 64-67.
  CrossrefPubMedGoogle Scholar
• 19 Mulders TA, Maurissen LFA, Meyer Z. et al. A positive family history for premature cardiovascular disease identifies patients prone to recurrent arterial thrombotic events. Eur J Prev Cardiol 2011; 19: 1465-1473.
  PubMedGoogle Scholar
• 20 Bushnell C, Siddiqi Z, Morgenlander JC. et al. Use of specialized coagulation testing in the evaluation of patients with acute ischaemic stroke. Neurology 2001; 56: 624-627.
  CrossrefPubMedGoogle Scholar
• 21 Morris JG, Singh S, Fisher M. Testing for inherited thrombophilias in arterial stroke. Can it cause more harm than good? Stroke 2010; 41: 2985-2990.
  PubMedGoogle Scholar
• 22 Putaala J, Haapaniemi E, Metso AJ. et al. Recurrent of ischaemic events in young adults after first-ever ischaemic stroke. Ann Neurol 2010; 68: 661-671.
  CrossrefPubMedGoogle Scholar
• 23 Rutten-Jacobs LCA, Maaijwee NAM, Arntz RM. et al. Long-term risk of recurrent vascular events after young stroke: the FUTURE study. Ann Neurol 2013; 74: 592-601
  CrossrefPubMedGoogle Scholar