CAC Doesn't Immediately Reverse When Risk Factors Improve

Reed Miller

November 15, 2011

November 15, 2011 (Orlando, Florida) — A new analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) shows that coronary artery calcium (CAC) levels do not track closely with changes in important coronary disease risk factors. This finding could have important implications for how risk-factor–modifying drugs are studied in the future, according to the lead author William Arguelles (University of Miami, FL).

Here at the American Heart Association 2011 Scientific Sessions, Arguelles told heartwire that "individuals who come in with a very high risk-factor profile and are the most likely to be placed on medications already have a very high underlying level of pathology that could be driving that calcification process independent of declines in risk factors," including blood pressure, lipid levels, and blood glucose. "Even though the blood pressure [for example] is declining, we know that these individuals have a longer history of hypertension and . . . medications and, therefore, a longer history of pathology independent of the declines in risk factors," he said.

CAC is a common measure of subclinical coronary disease associated with an increased number of coronary events, but the association between changes of common coronary disease risk factors and progression of CAC is not clear. So Arguelles and colleagues analyzed data from 6800 participants of the MESA study in six communities. All participants underwent a CAC imaging test with computed tomography at baseline and either 1.6 or 3.2 years later. A quarter of the study subjects also underwent a third CAC test at an average of 4.9 years after baseline.

The authors analyzed the how the changes in CAC over time were associated with changes in blood pressure and lipid levels. The analysis was adjusted for age, ethnicity, smoking status, family history of cardiovascular disease, total income as a marker of socioeconomic status, and previous use of hypertension, lipid, and glucose-lowering drugs.

Among men who had detectable CAC at baseline, CAC increased an average of 57 Agatston units/year. In women, CAC progressed by 39 Agatston units/year. In all patients, the risk-factor measures went up or down depending on whether they were taking antihypertensives, statins, or other medications.

In men, there was no statistical association between changes in risk factors and progression of CAC, and there was no link between changes in risk factors and CAC levels among men or women who did not have detectable CAC at baseline.

However, in women with CAC at baseline, there was an inverse relationship between declines in risk factors and an increase in CAC, such that women in whom the progression of risk factors and been slowed down or reversed showed the greatest increase in CAC over time.

"This was somewhat contrary to our hypotheses, so we did more analysis to look at the influence of medication use that might be driving these associations," Arguelles explained. For example, the analysis showed an inverse correlation between baseline systolic blood pressure and rate of hypertension change--so women who had the highest blood pressure levels at baseline showed the greatest improvement over time because those were the women who were most likely to be taking blood-pressure–lowering drugs. The women who were not on medication showed slower CAC progression, but there was no association between blood pressure and CAC in those patients. The same pattern of association was seen with low-density-lipoprotein levels and CAC.

"Our post hoc analysis suggests it's the medications that were driving these inverse findings, and they work to decrease these risk-factor levels, but not the increased rate of CAC," Arguelles explained.

He said that the influence of risk factors on the process of CAC "occurs in a time-lagged fashion" such that a longer study would have eventually seen CAC progression stop or reverse many years after the reversal in risk factors in patients taking medication. Whether risk factors such as high blood pressure and hyperlipidemia are more important to the initiation of calcification--or if they have more of a role in the progression of existing disease--is also not clear yet, he said. Also, the link between risk factors and CAC could be different for different subsets of patients.

Arguelles said that the next step in his group's research will be to "delve into how we conduct analysis on risk factors and disease, specifically stratifying individuals on medications," he told heartwire . "A lot of the analysis that we do, controlling for medications, and the way that we do it, doesn't really get us to a place where we can draw conclusions for different individuals. There could be differential effects for different subgroups of individuals, not only for their risk-factor status, but also on the medications they are taking."

Arguelles reported no conflicts of interest.


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