Associations Between C-Reactive Protein, Coronary Artery Calcium, and Cardiovascular Events: Implications for the JUPITER Population From MESA, a Population-Based Cohort Study

Study Questions:

Does coronary artery calcium (CAC) provide additional risk stratification to patients who have a similar risk profile to those subjects enrolled in the JUPITER (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) study?

Methods:

Patients enrolled in the MESA (Multi-Ethnic Study of Atherosclerosis) study were used for the present analysis. MESA is a population-based, prospective cohort study, which describes the prevalence, progression, and clinical significance of subclinical atherosclerosis. Between July 2000, and September 2002, MESA enrolled 6,814 individuals at six field centers in the United States (Baltimore; Chicago; Forsyth County, NC; Los Angeles; New York; and St. Paul, MN). Participants had to be between 45 and 84 years old, and have no known clinical cardiovascular disease at enrollment. From baseline data, 2,083 participants were identified who fit specific inclusion criteria for JUPITER: age 50 years and older for men and 60 years and older for women, low-density lipoprotein cholesterol <3.37 mmol/L, not on lipid-lowering therapy, free of diabetes, triglycerides <5.65 mmol/L, and creatinine <176.8 μmol/L. Of these participants, 950 (46%) had high high-sensitivity C-reactive protein (hs-CRP) (≥2 mg/L) and thus would have been eligible for JUPITER. Patients were stratified by CAC scores (scores of 0, 1–100, or >100). The primary outcomes of interest were new occurrences of coronary heart disease and cardiovascular disease.

Results:

A total of 950 participants met all criteria for JUPITER entry and were followed for a median of 5.8 years. Among the 444 subjects (44%) with a CAC score of 0, rates of CHD events were 0.8 per 1,000 person-years. For subjects with a CAC score from 1 to 100 (n = 267 [28%]), the coronary heart disease (CHD) event rate was 4.8 per 1,000 person-years. For subjects with a CAC score of more than 100 (n = 239 [25%]), rates of CHD events were 20.2 per 1,000 person-years. For CHD, the predicted 5-year number needed to treat (NNT) was 549 for a CAC score of 0, 94 for scores 1-100, and 24 for scores >100. For cardiovascular disease, the NNT was 124, 54, and 19. In the total study population, presence of CAC was associated with a hazard ratio of 4.29 (95% confidence interval, 1.99-9.25) for CHD, and of 2.57 (1.48-4.48) for cardiovascular disease. Hs-CRP was not associated with either disease after multivariable adjustment.

Conclusions:

The investigators concluded that CAC appears to further stratify risk among patients eligible for JUPITER, and may be helpful in identification of patients who have the most to benefit from statin therapy.

Perspective:

The MESA data allow for an excellent opportunity to examine both CAC and hs-CRP in terms of identification of those most likely to benefit from statins among patients who met enrollment criteria for JUPITER. As the authors point out, such research will assist in the appropriate allocation of resources such as statins.

Clinical Topics: Statins

Keywords: Fluorobenzenes, Coronary Disease, Baltimore, Pyrimidines, Los Angeles, New York, Calcium, C-Reactive Protein, Biological Markers, Chicago, Cardiovascular Diseases, Coronary Vessels, United States, Diabetes Mellitus, Sulfonamides


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