METHODS AND RESULTS: Plasma
cholesterol and 5
inflammation-sensitive
plasma proteins (ISP) (
fibrinogen, alpha1-antitrypsin,
haptoglobin,
ceruloplasmin, and
orosomucoid) were determined in 6063 healthy men, 28 to 61 years of age. The incidence of
stroke,
cardiac events (fatal and nonfatal), and cardiovascular deaths was compared between groups defined by levels of
cholesterol and ISP. Mean follow-up was 18.7 years. High ISP level was defined
as 2 to 5 ISP in the top quartile. High
cholesterol was associated with higher levels of ISP.
Hypercholesterolemia (> or =6.5 mmol/L, 251 mg/dL) was associated with an increased incidence of
ischemic stroke and
cardiac events and with a reduced incidence of
intracerebral hemorrhage. The ISP levels modified these associations. After risk factor adjustment, men with
hypercholesterolemia and high ISP levels had a significantly higher risk of cardiovascular death (relative risk [RR]=2.4; CI, 1.8 to 3.3),
cardiac events (RR=2.3; CI, 1.8 to 3.0), and
ischemic stroke (RR=2.1; CI, 1.4 to 3.3) than men with normal
cholesterol and low ISP levels. In the absence of high ISP levels,
hypercholesterolemia was associated with a moderately higher risk of cardiovascular death (RR=1.4; CI, 1.0 to 2.0) and
cardiac events (RR=1.5; CI, 1.2 to 1.9) but not significantly with
ischemic stroke (RR=1.25; CI, 0.8 to 2.0).
CONCLUSIONS: