Relation between homocysteine and non‐fatal stroke in peripheral arterial disease

Abstract

There are currently no data on whether high total serum homocysteine (tHcy) is predictive for cerebrovascular events in patients with symptomatic peripheral arterial disease (PAD). Therefore, the purpose of this study was to determine whether high tHcy levels were related to the evidence of non-fatal stroke in PAD. Evidence of non-fatal atherothrombotic stroke events was verified in 450 consecutive male patients, admitted for inpatient treatment of symptomatic PAD. The extent of carotid stenosis was evaluated by colour duplex Doppler measurement and fasting tHcy was determined by high-performance liquid chromatography. Within the population of 450 PAD patients a documented history of ischaemic stroke was evident in 50 subjects. The median tHcy values were significantly higher in PAD patients with stroke (18.6 micromol/l) than in PAD patients without stroke (15.1 micromol/l, P < 0.001). Logistic regression analysis revealed that tHcy was an independent and significant predictor (P=0.001) with an odds ratio (OR) of 1.37 for an increment of 5 micromol/l. In this multivariate model, diabetes mellitus (OR=2.34, P=0.011) and carotid stenosis > or =50% (OR=2.59, P=0.005) were also independently related to clinical cerebrovascular disease in PAD. In conclusion, the present study demonstrates an association of tHcy and evidence of non-fatal atherothrombotic stroke in patients with symptomatic PAD. This could be important, as a reduction of elevated tHcy concentrations by vitamin supplement might decrease the high frequency of cerebrovascular complications in PAD patients.

Hyperhomocysteinemia and Ischemic Stroke: A Potential Dose-Response Association—A Systematic Review and Meta-analysis

“…15 We report a similar increased risk of 43% (95% CI: 1.28-1.61) when standardizing reported ORs and using the same Hcy increments of 5 µmol/L. [18][19][20][21][22][23] The studies included in the present review assumed a linear association between Hcy levels and ischemic stroke; however, without describing this further or commenting on the hidden assumption of a linear association. As we observed a clear elevation in risk when surpassing 15 µmol/L, our results question this assumption of a linear association.…”

“…27,74 Moreover, Hcy levels have been shown to increase in critically ill patients. 120 In this review, no difference in means was observed when comparing Hcy levels in blood samples obtained during the acute phases 23,107,108,114,116 and convalescence phases of ischemic stroke 20,22,106,109 ; but based on the aforementioned previous studies, timing of blood sampling should be considered when evaluating Hcy as an exposure.…”

“…Of the 18 case-control articles rated as good, seven studies subclassified ischemic stroke 18,105-109 ; 1 reported CVD with subanalyses for ischemic stroke 19 and 10 studies performed no subclassification of ischemic stroke. 9,[20][21][22][23][110][111][112][113][114] The timing of blood sampling for measurement of Hcy levels varied among studies. Eight studies performed blood sampling prior to outcome 9,18,19,21,105,[110][111][112] ; 10 studies performed blood sampling after outcome, 20,22,23,[106][107][108][109][113][114][115] of which four studies collected blood within 7 days of outcome, 23,108,113,114 and 2 studies within 24 hours of outcome.…”

“…9,[20][21][22][23][110][111][112][113][114] The timing of blood sampling for measurement of Hcy levels varied among studies. Eight studies performed blood sampling prior to outcome 9,18,19,21,105,[110][111][112] ; 10 studies performed blood sampling after outcome, 20,22,23,[106][107][108][109][113][114][115] of which four studies collected blood within 7 days of outcome, 23,108,113,114 and 2 studies within 24 hours of outcome. 107,116…”

Endocrine intervention for transsexuals

“…Plasma levels of homocysteine, believed to be a modest (Homocysteine Studies Collaboration, 2002) or perhaps more significant (Graham et al ., 1998) independent cardiovascular and cerebrovascular risk factor (Haltmayer et al ., 2002) are reduced in hormone‐treated male‐to‐female transsexuals and increased in androgen treated female‐to‐male transsexuals (Giltay et al ., 1998). In practice, the additional risk of heart disease in people treated with cross‐sex hormones is not known but available data suggest that there is not a substantial increase (van Kesteren et al ., 1997).…”