C-reactive protein in 2005. Interview by Peter C. Block.

Acute coronary events strike nearly 1.4 million Americans annually. This includes an estimated 700,000 new coronary events, 500,000 recurrent events, and 175,000 silent first events each year. Adding to the clinical challenge is the fact that while conventional risk factors remain an important means of predicting who is at risk of developing coronary heart disease (CHD), it’s unwise to rely on conventional risk factors alone for estimating patient risk. A 2003 evaluation of 122,458 patients enrolled in 14 international trials was meant to underscore that conventional risk factors are still important, yet one in five men with CHD in these trials (n=87,869) had none of the four conventional risk factors analyzed: smoking, hypertension, diabetes, and hyperlipidemia. Another challenge: Despite the overwhelming effectiveness of HMG-CoA reductase inhibitors in lipid lowering, 60% to 70% of cardiovascular events continue to occur despite statin therapy. This is in stark contrast to a 1996 prediction that statin therapy might eliminate heart attacks by the year 2000. It should be noted that in the large review of international trials mentioned above, only 34.1% of men with CHD had hyperlipidemia. If the lipid hypothesis of atherosclerosis is still correct, why do so few CHD patients have hyperlipidemia and why are so many events still occurring in patients on statin therapy? The seemingly anomalous data have led investigators to question whether the accepted target levels for low-density lipoprotein (LDL) cholesterol are low enough. Recent trials, including REVERSAL and PROVE IT/TIMI-22, have shown that lower target LDL levels, particularly in high-risk patients, are effective in further reducing cardiovascular events. (The implications of these studies were discussed in a 2004 update of clinical guidelines.) Yet, even intensive statin therapy is not the complete answer. In the PROVE-IT TIMI-22 study, for example, high-dose statin therapy still was associated with a 25% recurrent event rate at 2.5 years.