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CARDIOLOGY
- Publications
CONTROLLING
HEART DISEASE
a
strategy update
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Fibrinogen
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Plasma fibrinogen is believed to be a strong risk factor
for atherosclerosis. Patients with CHD have elevated fibrinogen
levels and a stepwise increase of fibrinogen has been
reported as a function of the number of affected vessels.17
In prospective studies, plasma fibrinogen, strongly associated
with triglyceride levels, was found to be an independent
predictor for myocardial infarction.18 Plasma
fibrinogen levels provides information of CHD risk over
and beyond that supplied by established risk factors.
At present, there is no evidence to show that the decrease
in fibrinogen brings about a decrease of cardiovascular
risk. However, the combined reduction of both cholesterol
and fibrinogen might be more useful than the simple reduction
of cholesterol, in preventing CHD.
In clinical studies, statins have
been associated with either no change, or a slight increase
in fibrinogen levels.19,20 Fibrates have been
shown to exhibit different effects on plasma fibrinogen.
While fenofibrate and bezafibrate have been shown to decrease
fibrinogen levels, gemfibrozil has been shown to increase
fibrinogen levels in some studies.17
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| Lipoprotein
(a) |
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Lp (a) is a lipoprotein that is similar in structure
to LDL but is characterized by the presence of an additional
protein called apolipoprotein (a) which is linked by
a single disulfide bond to apo B. Lp (a) levels are
highly genetically determined. A large body of epidemiologic
data supports an independent association between elevated
plasma levels of Lp (a) and atherosclerotic vascular
disease.8
Statins have no effect in lowering Lp (a). Nicotinic
acid is the only lipid-lowering drug that consistently
lowers the Lp (a) level. Micronised fenofibrate has
also been shown to reduce Lp (a) levels by 7 to 23%.
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| Beyond
LDL reduction: The Fibrate Renaissance |
Micronised fenofibrate is an effective lipid-regulating
agent, which causes a decrease in LDL and total cholesterol
levels, a marked reduction in elevated triglycerides and
an increase in HDL levels.
In clinical trials, micronised fenofibrate 200 mg once
daily was of similar efficacy to or less effective than
the statins, simvastatin 20 mg daily and pravastatin 20
mg daily at reducing LDL and total cholesterol levels.
However, fenofibrate produced greater improvements in
triglyceride and HDL levels than statins. Micronised fenofibrate
has also been shown to reduce fibrinogen levels, Lp (a)
and serum uric acid levels.
Micronised fenofibrate is well tolerated. Gastrointestinal
disorders are the most frequent adverse events associated
with therapy. Elevations in serum transaminase and creatine
phosphokinase levels have been reported rarely with micronised
fenofibrate.
The use of fibrates, such as fenofibrate, would help in
countering other CHD risk factors and therefore play a
central role in the effective management of CHD.
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| Conclusion |
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The magnitude of risk reduction achieved by targeting
LDL averages around 30%, clearly indicating that there
is a need to consider additional possible therapy that
goes beyond LDL lowering to optimize the management
of CHD risk in a significant proportion of patients.
Evidence strongly suggests that additional or alternative
intervention with other lipid altering therapies, such
as fibrates may be necessary.
References
(1) Lancet 1999; 344: 1383-1389. (2) N Engl J Med 1995;
333: 1301-13070. (3) N Engl J Med 1996; 335: 1001-1009
(4) Am J Cardiol 2001; 88 (suppl): 1N-2N (5) European
Heart Journal 1998; 19 (suppl M): M8-M14 (6) Am J Cardiol
1999; 83: 3F-12F (7) J Cardiovasc Risk 1996; 3: 213-219.
(8) Med Clin N Am 2000; 84: 43-61 (9) Third Report of
the National Cholesterol Education Program (NCEP) Expert
Panel on Detection, Evaluation and Treatment of High
Blood Cholesterol in Adults. NIH Publication No. 01-3670;
May 2001
(10) Am J Cardiol 2001; 88 (suppl): 9N-13N (11) Am J
Cardiol 2001; 88 (suppl): 19N-23N (12) Am J Cardiol
2001; 88 (suppl): 41N-44N (13) Metabolism 1993; 42:
1461-1467 (14) Circulation 1996; 94: 2146-2153 (15)
Circulation 1997; 95: 69-75 (16) Vnitr Lek 1999; 45:
441-443 (17) Thrombosis and Haemostasis 1999; 70: 241-243
(18) Eur J Clin Pharmacol 2000; 56: 631-635 (19) Clin
Drug Invest 1998; 16: 219-226
(20) Am J Cardiol 2000; 85: 350-353 (21) Drugs 1997;
54: 615-633
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