Key result
Elevated homocysteine shows no association with cardiovascular autonomic function regardless of glucose tolerance.
Why the study?
The mechanism by which homocysteine causes cardiovascular disease is unknown, leaving it unclear whether hyperhomocysteinaemia is associated with impaired cardiovascular autonomic function in elderly individuals across glucose tolerance categories.
Is hyperhomocysteinaemia associated with impaired cardiovascular autonomic function in elderly Caucasian subjects with normal glucose metabolism, impaired glucose metabolism, or type 2 diabetes?
Cross-Sectional (n=609)
Is hyperhomocysteinaemia associated with impaired cardiovascular autonomic function in elderly Caucasian subjects with normal glucose metabolism, impaired glucose metabolism, or type 2 diabetes?
Cardiovascular autonomic dysfunction is not associated with homocysteine levels in diabetic or nondiabetic elderly subjects and therefore does not explain the link between hyperhomocysteinaemia and cardiovascular mortality.
No association observed; does not support autonomic dysfunction as mediator of homocysteine-related cardiovascular risk and leaves other pathways open.
OBJECTIVE: Homocysteine and cardiovascular autonomic function are both predictors of cardiovascular disease and death, particularly in patients with diabetes. The mechanism by which homocysteine causes disease is unknown. The objective of our study was to determine whether hyperhomocysteinaemia is associated with impaired cardiovascular autonomic function in an age-, sex-, and glucose tolerance-stratified sample of an elderly Caucasian population. METHODS: We studied 609 subjects, 252 with normal glucose metabolism, 173 with impaired glucose metabolism, and 184 with type 2 diabetes. Cardiac cycle duration (RR interval) and continuous finger arterial pressure were measured under three conditions: during (i) spontaneous breathing, (ii) six deep breaths over 1 min, and (iii) an active change in position from lying to standing. From these readings, 10 parameters of autonomic function were assessed (three Ewing tests, six heart rate variability tests and one test of baroreflex sensitivity). These 10 measurements were summarized in a single cardiovascular autonomic dysfunction score (CADS). RESULTS: Comparing values of autonomic function measures in the lowest versus the highest quartile of homocysteine revealed no significant association between homocysteine level and autonomic function in the whole study group, nor in the individual glucose tolerance groups. Multiple adjustment for age, sex, waist-to-hip ratio, serum creatinine, use of antihypertensives and fasting insulin, confirmed this result. We found no evidence of effect modification of glucose tolerance status on the association between homocysteine and autonomic dysfunction (P for interaction for CADS = 0.79). CONCLUSIONS: There is no evidence for an association between homocysteine levels and cardiovascular autonomic function in either diabetic or nondiabetic subjects. Cardiovascular autonomic dysfunction does not help explain why hyperhomocysteinaemia is related to cardiovascular mortality.
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Man et al. (2005) conducted a cross-sectional in Normal glucose metabolism, impaired glucose metabolism, or type 2 diabetes mellitus (n=609). Highest quartile of homocysteine level vs. Lowest quartile of homocysteine level was evaluated on Cardiovascular autonomic dysfunction score (CADS) summarizing 10 parameters of autonomic function (three Ewing tests, six heart rate variability tests, and one test of baroreflex sensitivity). Homocysteine levels (highest vs lowest quartile) showed no significant association with cardiovascular autonomic function across glucose tolerance groups (P for interaction for CADS = 0.79).
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