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More evidence links MCP-1 levels to cardiovascular mortality

JAMA Cardiology
Reuters Health - 12/11/2020 - Higher circulating levels of monocyte-chemoattractant protein-1 (MCP-1) are associated with higher long-term cardiovascular mortality in individuals free of overt heart disease, a meta-analysis suggests.

"By complementing evidence from previous genetic and experimental studies, these results provide additional support for a key role of MCP-1 in cardiovascular disease development," note Dr. Martin Dichgans of Ludwig-Maximilians-University in Munich and colleagues in JAMA Cardiology.

The meta-analysis included seven cohort studies involving more than 21,000 individuals without known heart disease (mean age, 54; 47% men). Mean follow-up was 15.3 years.

In adjusted models (age, sex, race/ethnicity), higher baseline MCP-1 levels were associated with increased risk of coronary heart disease (hazard ratio per one standard-deviation increment in MCP-1 levels, 1.06), nonfatal myocardial infarction (HR, 1.07), and cardiovascular death (HR, 1.12). In MCP-1 quartile analyses, the associations followed dose-response patterns.

After additional adjustment for vascular risk factors, the risk estimates were attenuated, but the associations between MCP-1 levels and cardiovascular death remained statistically significant, as did associations in the upper quartile with coronary heart disease.

No significant heterogeneity was seen and the results did not change in sensitivity analyses excluding events occurring in the first five years after MCP-1 measurement. Further, risk estimates were stable after additional adjustments for circulating levels of interleukin-6 and high-sensitivity C-reactive protein (hsCRP).

However, the authors note, "The magnitude of the examined associations was modest, and there was no increment in C-statistics for MCP-1 on top of other vascular risk factors for prognosticating cardiovascular disease. Thus, MCP-1 measurement is unlikely to be a valuable risk marker for cardiovascular end points," but might be considered "as a promising target in atherosclerosis."

Dr. Richard Gumina, Associate Division Director for Research in the Division of Cardiovascular Medicine at The Ohio State University Wexner Medical Center in Columbus, commented in an email to Reuters Health. "If we extrapolate that elevated MCP-1 levels are indicative of a proinflammatory milieu," he said, "these data build upon prior work examining hsCRP, IL-6 and IL-1 beta, to support that heightened inflammation contributes to cardiovascular disease."

"The finding that the risk estimates for MCP-1 levels were stable after adjustment for IL-6 and hsCRP point suggests that MCP-1 contributes to cardiovascular risk via different mechanisms," he said. "However, the magnitude of the MCP-1 associations was modest."

"Importantly, MCP-1 levels did not provide a significant increment on top of the assessment of known vascular risk factors (hypertension, low-density lipoprotein cholesterol levels, use of statins, diabetes mellitus, body mass index, smoking, estimated GFR, physical activity and alcohol consumption)," he said. "Thus, using MCP-1 levels as a risk marker for cardiovascular endpoints is not supported at this time."

"Whether MCP-1 represents a viable target to attenuate the inflammation that drives atherosclerosis and contributes to cardiovascular mortality is an interesting hypothesis that requires further evaluation," he added. "Future studies will be needed to determine if decreasing MCP-1 levels impacts cardiovascular mortality."

Dr. Elsa-Grace Giardina, Director, Center for Women's Health in the Division of Cardiology at Columbia University Irving Medical Center in New York City also commented by email. "The authors describe limitations to the report, including a lack of a standardized assay to quantify MCP-1," she told Reuters Health. "The exploratory findings support the view that further evaluation is merited using a standardized assay."

"It is also noteworthy that only three of the seven sites were from the US, where risk factors such as obesity and inadequately treated hypertension might be even more prevalent than in the United Kingdom, Germany, Sweden, and the Netherlands," she noted. "A prospective US study is indicated."

"Additional studies, such as a placebo-controlled novel drug intervention against MCP-1, could be useful to guide primary and secondary prevention for cardiovascular disease," she added.

Dr. Dichgans did not respond to requests for a comment.

By Marilynn Larkin

SOURCE: https://bit.ly/3eSSO4F JAMA Cardiology, online November 4, 2020.

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