Homocysteine thiolactone and other sulfur-containing amino acid metabolites are associated with fibrin clot properties and the risk of ischemic stroke

Homocysteine (Hcy) and Hcy-thiolactone (HTL) afect fbrin clot properties and are linked to
cardiovascular disease. Factors that infuence fbrin clot properties and stroke are not fully
understood. To study sulfur-containing amino acid metabolites, fbrin clot lysis time (CLT) and
maximum absorbance (Absmax) in relation to stroke, we analyzed plasma and urine from 191
stroke patients (45.0% women, age 68 ± 12 years) and 291 healthy individuals (59.7% women, age
50 ± 17 years). Plasma and urinary levels of sulfur-containing amino acid metabolites and fbrin clot
properties were signifcantly diferent in stroke patients compared to healthy individuals. Fibrin CLT
correlated with fbrin Absmax in healthy males (R2 = 0.439, P= 0.000), females (R2 = 0.245, P= 0.000),
female stroke patients (R2 = 0.187, P= 0.000), but not in male stroke patients (R2 = 0.008, P=ns). Fibrin
CLT correlated with age in healthy females but not males while fbrin Absmax correlated with age in
both sexes; these correlations were absent in stroke patients. In multiple regression analysis in stroke
patients, plasma (p)CysGly, pMet, and MTHFR A1298C polymorphism were associated with fbrin
Absmax, while urinary (u)HTL, uCysGly, and pCysGly were signifcantly associated with fbrin CLT. In
healthy individuals, uHTL and uGSH were signifcantly associated with fbrin Absmax, while pGSH, and
CBS T833C 844ins68 polymorphism were associated with fbrin CLT. In logistic regression, uHTL, uHcy,
pCysGly, pGSH, MTHFR C677T polymorphism, and Absmax were independently associated with stroke.
Our fndings suggest that HTL and other sulfur-containing amino acid metabolites infuence fbrin clot
properties and the risk of stroke.