Homocysteine increases the risk associated with hyperlipidaemia.
BACKGROUND
The European Concerted Action Project 'Homocysteine and Vascular Disease' showed that an elevated homocysteine is associated with a substantially increased risk of cardiovascular disease, and particularly when combined with other factors such as smoking, hypertension and hypercholesterolaemia. The purpose of this study was to examine the potential interactions between homocysteine and individual lipid subfractions. In addition, it was hypothesized that HDL cholesterol may protect against hyperhomocysteinaemia because HDL cholesterol is associated with the enzyme paroxonase, which reduces oxidization of homocysteine to the harmful metabolite, homocysteine thiolactonase.


METHODS
Data from a multicentre European case-control study (750 cases and 800 controls) were used for analysis. The risks of vascular disease associated with homocysteine, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, apoprotein A1 and apoprotein B were established. The effect of elevated homocysteine on the cardiovascular risk associated with each lipid subfraction was then examined.


RESULTS
As expected, homocysteine, total cholesterol, LDL cholesterol, triglycerides and apolipoprotein B were associated with cardiovascular risk. HDL cholesterol was inversely related to risk. Homocysteine increased the risk associated with all lipid measures. In contrast, a low plasma cholesterol does not seem to confer protection against the risk associated with a raised plasma homocysteine. Hyperhomocysteinaemia is associated with an increased risk at all levels of HDL cholesterol, conversely, in those with elevated homocysteine HDL cholesterol levels result in reduced risk.


CONCLUSIONS
In general, the increased cardiovascular risk associated with elevated homocysteine is evident across the spectrum cholesterol subfraction levels.
Daly
Caroline
C
Royal Brompton Hospital, Sydney St, London, UK.
Fitzgerald
Anthony P
AP
O'Callaghan
Patrick
P
Collins
Patrick
P
Cooney
Marie Therese
MT
Graham
Ian M
IM
D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000209:etiology*; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005060:Europe; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications*; D006949:Hyperlipidemias / Q000097:blood / Q000150:complications*; D008055:Lipids / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010865:Pilot Projects; D018570:Risk Assessment; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation
C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008055:Lipids; D014280:Triglycerides; D006710:Homocysteine