Abstract
It is not known how total homocysteine (tHcy) levels change during the transition from acute stroke to post-stroke convalescence or whether tHcy changes occurring after the acute period are associated with recurrence of cerebro-cardiovascular events. Levels of tHcy were measured during acute ischemia and again after three months. Patients were followed for a median of 18 (range: 12–36) months. A total of 2800 patients who had at least two tHcy measurements were enrolled between February 2012 and June 2014; 2587 patients presented with ischemic stroke and 213 presented with cerebral hemorrhage. During the follow-up period, 220 (7.9%) patients experienced another ischemic event. After adjusting for additional cardiovascular risk factors, patients with the highest levels of tHcy (fourth quartile; >15.5 μmol/L) had a 1.76-fold increased risk of a recurrence (adjusted HR: 1.76, 95%CI: 1.11–3.08) as compared to patients with the lowest levels of tHcy (lowest quartile; ≤9.65 μmol/L). Additional analysis by subgroup indicated that this correlation was only significant for patients with large-artery atherosclerosis ischemia (adjusted HR: 2.00, 95%CI: 1.13–3.55). Elevated tHcy during the convalescent phase of acute stroke was independently associated with an increased risk of recurrent ischemic stroke, especially in those patients with large-vessel atherosclerosis ischemia.
Highlights
Accumulating data suggest elevated total serum homocysteine is associated with an increased risk of coronary heart disease and stroke[1,2,3,4,5]
After analyzing the data by type of ischemia, we found that patients with large-artery atherosclerosis ischemia with high levels of total homocysteine (tHcy) had a significantly higher risk of recurrent ischemic stroke than patients in the lowest quartile
The rate of recurrence of an ischemic event was significantly higher in patients in the fourth tHcy quartile than in patients in the first quartile, even after adjusting for potential clinically relevant confounders; the association was especially prominent in those patients suffering from large-artery atherosclerosis
Summary
Accumulating data suggest elevated total serum homocysteine (tHcy) is associated with an increased risk of coronary heart disease and stroke[1,2,3,4,5]. If stroke results in an increased tHcy level after the event, the observed elevated post stroke levels among stroke “cases” may lead to misguided conclusions regarding the role of tHcy as a risk factor for the development of the stroke It could be, as some suggest, that elevated tHcy is an acute-phase reactant and a consequence rather than a cause of the disease process[11,12]. THcy levels have been shown to increase between the acute period and after several months of convalescence after the original ischemic event[13,14]. This study allows us to analyze whether elevated plasma tHcy levels occurring during the convalescent period after an acute ischemic event contribute to the risk of recurrence
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