Low-density lipoprotein particles and risk of intracerebral haemorrhage in subjects with cerebrovascular disease.
BACKGROUND
Only limited data are available for risk factors for intracerebral haemorrhage (ICH) in subjects with established cerebrovascular disease.


METHODS
We performed a nested case-control study of participants of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS). This was a randomized, placebo-controlled trial that established the beneficial effects of blood pressure lowering in 6105 patients with cerebrovascular disease.


METHODS
Each of 41 subjects who experienced ICH during a mean follow-up of 3.9 years was matched to 1-3 control subjects. Lipoprotein particles and other plasma markers were measured in baseline blood samples from PROGRESS participants.


RESULTS
In comparison with control subjects, ICH cases had increased mean low-density lipoprotein (LDL) diameter (P=0.04) and increased large LDL particle concentration (P=0.03). The odds ratio (adjusted for regression dilution bias) for ICH risk with 10 mmHg increase in systolic blood pressure (SBP) was 1.45 (95% confidence interval: 1.01-2.09, P=0.05), with a 1 nm increase in mean LDL diameter it was 2.15 (95% confidence interval: 0.97-4.77, P=0.06), and with 100 nmol/l increase in large LDL particle concentration it was 1.18 (95% confidence interval: 0.98-1.43, P=0.08). Plasma levels of C-reactive protein (CRP), soluble vascular cell adhesion molecule 1 (sVCAM-1), homocysteine, amino-terminal-pro-B-type natriuretic peptide (NT-proBNP), and renin were not associated with ICH risk.


CONCLUSIONS
SBP predicted ICH risk in subjects with cerebrovascular disease, whereas CRP, sVCAM-1, homocysteine, NT-proBNP, and renin did not predict ICH risk. The trends for prediction of ICH risk by mean LDL particle diameter and large LDL particle concentration are hypothesis generating and require confirmation in larger studies.
Campbell
Duncan J
DJ
St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia. dcampbell@svi.edu.au
Neal
Bruce C
BC
Chalmers
John P
JP
Colman
Samuel A
SA
Jenkins
Alicia J
AJ
Kemp
Bruce E
BE
Patel
Anushka
A
Macmahon
Stephen W
SW
Woodward
Mark
M
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D016022:Case-Control Studies; D002543:Cerebral Hemorrhage / Q000097:blood / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D002561:Cerebrovascular Disorders / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010316:Particle Size; D020913:Perindopril / Q000627:therapeutic use; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D055502:Secondary Prevention; D013599:Systole
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D015415:Biomarkers; D008077:Lipoproteins, LDL; D020913:Perindopril