Biomarkers predictive of inflammatory processes in acute clinical settings

New Information Which Expands The Universe Of People Who Should Be Taking Crestor (4/1/10)

Charles J. Glueck MD, Jewish Hospital Cholesterol Center, email glueckch@healthall.com, cglueck@fuse.net, phone 513-924-8250.

The relevance of the new data on  high sensitivity C-reactive protein (HSCRP) is as follows:

1. In adults (>50 men, >60 women), with HSCRP >2, and one other risk factor for heart attack or stroke (high cholesterol, high blood pressure, type 2 diabetes), the most potent statin, Crestor, is indicated with a goal of lowering LDL cholesterol well below 100 mg/dl, to protect against heart attack and stroke. This is indicated even if the LDL cholesterol is “normal” , ≥ 100 mg/dl
2. Although HSCRP is not itself a direct risk factor for heart attack and stroke, it is an indicator of inflammation, and treatment with Crestor will usually lower HSCRP levels < 1, which would be ideal.

Biomarkers predictive of inflammatory processes in acute clinical settings (e.g., during infection or after traumas) have become valuable predictors of future vascular events.¹ This primal organism-response to invading pathogens, trauma or chronic inflammation presumably represents a protective mechanism and involves a cascade of thrombotic and inflammatory factors of variable expression.¹ In the chronic state, acute phase reactants have become important predictors of future vascular events: thus, baseline serum high sensitivity c-reactive protein (hsCRP) values have been correlated with the development of CHD in healthy men1, 2  and women1  in the Harvard Study population, corroborated by other groups.^{3, 4}  A meta-analysis of 11 population based cohort studies with a total of 1,953 subjects and 3 investigations of 604 subjects with pre-existing vascular disease revealed hsCRP-related risk ratios of 2.0 and 1.5 respectively, while for hsCRP overall the risk ratio was 1.9 (95% CI 1.5-2.3).⁵

In adults, statins lower hsCRP concurrently with LDL cholesterol, and hsCRP levels achieved on statin therapy are predictive of CVD event rates irrespective of the lipid endpoint used.⁶ To test the hypothesis whether or not subjects with normal low-density lipoprotein cholesterol but elevated CRP represent a population at increased risk that might benefit from statin treatment, the JUPITER trial⁶ randomized 17,802 apparently healthy persons to either 20 mg Rosuvastatin daily or placebo. The rates of the primary endpoint (composite of nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, revascularization, and confirmed death from cardiovascular causes) were 0.77 and 1.36 per 100 person-years of follow-up in the Rosuvastatin and placebo groups, respectively. Relative risk reduction was 44%.⁶ CRP may have more accurately selected high-risk subjects due to its association with multiple risk factors, thus representing an aggregate-integrative marker of the total inflammatory burden of an individual.⁶  

References

1. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000;342:836-43.
2. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997;336:973-9.
3. Kuller LH, Tracy RP, Shaten J, Meilahn EN. Relation of C-reactive protein and coronary heart disease in the MRFIT nested case-control study. Multiple Risk Factor Intervention Trial. Am J Epidemiol 1996;144:537-47.
4. Koenig W, Sund M, Frohlich M, et al. C-Reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992. Circulation 1999;99:237-42.
5. Danesh J, Whincup P, Walker M, et al. Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses. BMJ 2000;321:199-204.
6. Ridker PM, Danielson E, Fonseca FA, et al. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet 2009;373:1175-82.