As insulin goes up so does the danger of arterial plaques

Most readers of these posts, practitioner and layperson alike, have probably long been aware of the role of insulin resistance in cardiovascular disease, chronic inflammation and cancer as described in last week's New York Times article. A fascinating study that adds to the mountain of scientific evidence was just published in the Public Library of Science (PLoS One) in which the authors show that higher insulin levels are associated with the unstable form of carotid artery plaque:

"The stability of atherosclerotic plaques determines the risk for rupture, which may lead to thrombus formation and potentially severe clinical complications such as myocardial infarction and stroke. Although the rate of plaque formation may be important for plaque stability, this process is not well understood. We took advantage of the atmospheric 14C-declination curve (a result of the atomic bomb tests in the 1950s and 1960s) to determine the average biological age of carotid plaques."

The authors dissected the cores of carotid plaques from 29 patients with carotid stenosis and analyzed them for 14C. Their findings are fascinating:

"The average plaque age (i.e. formation time) was 9.6±3.3 years. All but two plaques had formed within 5–15 years before surgery. Plaque age was not associated with the chronological ages of the patients but was inversely related to plasma insulin levels...plaques in the lowest tercile of plaque age (most recently formed) were characterized by further instability with a higher content of lipids and macrophages...Microarray analysis of plaques in the lowest tercile also showed increased activity of genes involved in immune responses and oxidative phosphorylation."

As readers here know, a heart attack or stroke occurs when a vulnerable plaque ruptures and blocks a smaller vessel downstream. These investigators show that unstable plaque is associated with higher insulin levels. Intervening to reduce insulin resistance is one of the most important things that clinicians and patients can do for a host of conditions. The authors conclude:

"Our results show, for the first time, that plaque age, as judge[d] by relative incorporation of 14C, can improve our understanding of carotid plaque stability and therefore risk for clinical complications. Our results also suggest that levels of plasma insulin might be involved in determining carotid plaque age."

Regarding laboratory testing to determine the presence of inflamed vulnerable plaque, see the earlier post on Lp-PLA2.