Coronary Calcium Weeds Out JUPITER-Like Patients

November 23, 2010

November 23, 2010 (Chicago, Illinois) — Roughly half of patients meeting the criteria for statin therapy based on Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) have a low risk of cardiovascular events when assessed with coronary artery calcium (CAC) imaging scans, according to the results of a new study. Among patients with calcification of the coronary artery, the risk of cardiovascular events was significantly greater than those without calcification, suggesting that CAC assessed by computed tomography (CT) might be used to further stratify at-risk patients for statin therapy.

"We took patients who fit the JUPITER criteria, so they had high CRP levels, and wanted to see if coronary calcium could further risk-stratify these patients, and it does tremendously well," lead investigator Dr Michael Blaha (Johns Hopkins Medical Institute, Baltimore, MD) told heartwire . "If you fit the JUPITER criteria, which is sort of an older population, and you have no coronary calcium, your event rate is so low that you can't expect to get much from a statin in terms of event reduction in the next five to 10 years. The other patients we saw had calcium, with 25% of patients having the most calcium, and their event rate was 20 times that observed in patients without calcification."

The analysis was presented earlier this week at the American Heart Association (AHA) 2010 Scientific Sessions.

When it was published and presented two years ago, JUPITER created quite a stir, particularly since the trial showed that patients with normal LDL-cholesterol levels but with other risk factors would be eligible for statin therapy. At the time, some researchers attempted to put hard numbers on these newly eligible patients, with one study suggesting that roughly one in five middle-aged men and women would be eligible for statin therapy, while another showed that about 6.5 million people would be eligible for the lipid-lowering drugs.

"The threshold for statin therapy has come down and down, with JUPITER suggesting that even people with normal LDL-cholesterol levels--and of course high-sensitivity C-reactive protein [hs-CRP] levels--should be on statins," said Blaha. "But the absolute risk reduction in these trials is pretty low. We wanted to find a way to figure out who would really benefit from statins, and because we work with subclinical atherosclerosis, we wanted to see if coronary calcium, in particular, could further risk-stratify the JUPITER patient."

Putting JUPITER Into MESA

In the study, Blaha and colleagues examined the association between high hs-CRP levels, defined as >2 mg/dL, coronary calcium, and cardiovascular events in the Multi-Ethnic Study of Atherosclerosis (MESA). Of 6814 patients in MESA, they identified 2083 patients who met the criteria for JUPITER. These patients, 40% of whom were female, were 67 years old, with hs-CRP levels of 4.3 mg/dL and a mean 10-year risk Framingham risk score of 10%.

Almost half of patients in the MESA cohort had no coronary calcification assessed by CT. Among those with a CAC of zero, the number-needed-to-treat (NNT) was 549 to prevent one coronary heart disease event and 124 to prevent one cardiovascular disease event. Most events occurred in individuals with a CAC >100, and among these patients the NNT to prevent one coronary heart disease and cardiovascular disease event was 24 and 19, respectively.

Events by CAC Stratification

CAC Group Patients, n (%) Events, n (%) Event Rate (per 1000 person-years) Hazard Ratio (95% CI)
Coronary Heart Disease        
 CAC=0 444 (47) 2 (0.5) 0.8 1.0 (reference)
 CAC 1–100 267 (28) 7 (3) 4.8 4.6 (0.9-23.4)
 CAC >100 239 (25) 25 (11) 20.2 24.8 (5.4-11.5)
Cardiovascular Disease Events        
 CAC=0 444 (47) 9 (2) 3.7 1.0 (reference)
 CAC 1–100 267 (28) 12 (5) 8.4 1.8 (0.7-4.6)
 CAC >100 239 (25) 32 (13) 26.4 6.0 (2.5-14.6)


"JUPITER opens up millions of patients in the statin algorithm," Blaha told heartwire . "We're suggesting that if you look at who's really expected to benefit, these people actually have measurable disease."

In a second analysis comparing hs-CRP vs CAC for risk prediction, the group found that CRP did not predict events after adjustment for other risk factors among the 2083 MESA patients who met the criteria for JUPITER. CAC, on the other hand, had a strong relationship with clinical events, regardless of CRP status.

CAC vs hs-CRP for Risk Prediction

Variable Coronary Heart Disease Events, HR (95% CI) Cardiovascular Disease Events, HR (95% CI)
hs-CRP <2 mg/dL 1.0 (reference) 1.0 (reference)
hs-CRP >2 mg/dL 0.9 (0.5-1.5) 1.1 (0.7-1.6)
CAC=0 1.0 (reference) 1.0 (reference)
CAC 1–100 1.7 (0.7-4.2) 1.5 (0.8-2.8)
CAC >100 9.0 (4.0-20.3) 4.4 (2.4-7.9)


To heartwire , Blaha said the lack of association between high CRP levels and adverse events raises questions about how useful CRP is in a population with multiple ethnicities. Although studies, including his own, have shown the strength of CAC scores for predicting adverse events, he said the imaging test is not for everyone. It could be used as a tie-breaker for statin therapy in low- to intermediate-risk patients, those with normal cholesterol levels but other risk factors, including high levels of CRP.

"We think that it is time to move past traditional risk factors and serum biomarkers and toward incorporation of measures of subclinical atherosclerosis in risk prediction," said Blaha. "This makes sense because we are directly measuring the disease we propose to treat with statins.  Measuring subclinical atherosclerosis can help determine who is more likely to benefit from statins and who is unlikely to benefit. . . . We are not saying that everybody needs a CAC scan. However, it is very helpful in asymptomatic patients in whom the question of statin benefit is uncertain."

CRP took another hit at this week's AHA meeting in a presentation of a post hoc analysis of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) lipid-lowering arm, when investigators showed that the addition of hs-CRP measurements didn't improve conventional risk assessments in patients with hypertension and other CV risk factors who had normal or only modestly elevated LDL-cholesterol levels. In that analysis, reported by heartwire , neither baseline nor on-treatment CRP levels provided useful information about the efficacy of statin treatment to reduce cardiovascular events beyond LDL-cholesterol reduction.

Blaha reports no conflicts of interest. The analysis is supported by grants from the National Institutes of Health.

The complete contents of Heartwire , a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.

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