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Clogged Arteries

by Regina Patrick, RPSGT

The relationship between insufficient sleep and coronary artery disease.

Coronary artery calcification is a risk factor for developing coronary heart disease. Calcification is the deposit of calcium salts within a tissue. The deposits are called plaques. Some factors that can precede the development of coronary artery calcification are obesity, high blood pressure, and glucose intolerance. In recent years, scientists have found that sleep duration may be another factor that precedes the formation of calcium plaques.

The heart has one left and one right coronary artery. Each originates from the base of the aorta. From there, they branch and encircle the base of the heart in a crown-like fashion. They supply the musculature of the heart's ventricles and atria with blood. Normally, the coronary arteries are very elastic, which enables blood to pass through them easily. Calcium plaques stiffen the walls of these arteries, making it more difficult for blood to pass through. Calcium plaques can be associated with fatty deposits that can develop and enlarge within the wall of an artery. The fatty plaque may over time bulge into the artery, slowly blocking bloodflow, or it may dislodge and travel to a narrower portion of a vessel and block bloodflow. The result can be a heart attack.


Recent studies indicate an association between short sleep duration and the development of coronary plaque.1 However, several of these studies involved hypertensive subjects and the researchers did not distinguish whether sleep deprivation alone, hypertension alone, or the combination of the two resulted in the increased calcification of the coronary arteries. In addition, the quantity of sleep was based on self-report, which may have biased the results. To address this issue, Christopher King2 and associates used actigraphy in their recent study to objectively measure study participants' sleep duration, and they used computed tomography (CT) to assess the presence of calcification. Actigraphy uses movement to determine a person's wake and sleep cycles and is based on the premise that the greatest amount of body movement occurs during wake and the least amount occurs during sleep. A watch-like monitor records the wearer's level of body movements. The study participants underwent a baseline study. Five years later, they were reassessed and the results were compared.

At the baseline study, 7.5% of the subjects had detectable coronary artery calcification. Five years later, nearly 19% of the subjects had detectable calcification. Based on statistical analyses of six sleep duration categories (less than 4 hours; 4 to 5 hours; 5 to 6 hours; 6 to 7 hours; 7 to 8 hours; and more than 8 hours), the researchers noted that the calcification incidence (the number of people who developed calcification for the first time) fell as the sleep period increased. Statistical analyses also determined that increasing sleep by an hour reduces the odds of developing coronary calcification by 33%. King concluded that a short sleep duration increases the risk of developing coronary artery calcification.


Scientists are not sure how coronary calcification develops. Various researchers have noted an increased number of inflammatory cells and inflammatory factors in calcified coronary artery samples.3-5 A possible explanation for this finding is that chronic stress (for example, improper levels of blood glucose) on the outermost layer of the artery triggers a low grade inflammatory response.6 This induces macrophages (a type of white blood cell) within the arterial wall to secrete inflammatory substances such as tumor necrosis factor (TNF), interleukin-6 (IL-6), and adipokines. Increased levels of these inflammatory substances may then induce the development of calcium plaques.

Some scientists suspect oxidative stress may play a role in arterial calcification. Oxidative stress is impaired cellular metabolism resulting from the presence of an excessive amount of tissue-damaging molecules or from an insufficient amount of antioxidants. Oxidative stress apparently modulates the production of osteogenic factors that transform vascular smooth muscle cells into bone-like tissue. For example, researchers Chang Hyung Byon7 and colleagues in their in vitro study found that exposing vascular smooth muscle cells from the rat aorta to hydrogen peroxide (an oxidative by-product of cellular metabolism) resulted in the cells producing dramatically more bone markers than muscle markers. They concluded that oxidative stress induces the expression of bone markers, thereby promoting the development of calcium plaques in vascular smooth muscle cells.

Genetic researchers have noted an increased production of osteogenic transcription factors in calcified arterial samples.8 The increased production means that there is also an increased production of genes that encode for mineralization-regulating proteins.

A final possibility for the formation of coronary artery calcification may be the impaired differentiation of calcifying vascular cells, a type of vascular smooth muscle cell. Calcifying vascular cells exist in the muscular layer of a blood vessel. In in vitro studies, these cells express chemicals associated with their transformation into bone tissue. The expression of these chemicals is similar to that found in skeletal bone. The improper transformation of calcifying vascular cells leading to arterial calcification may result from either decreased amounts of chemicals that inhibit the expression of osteogenic chemicals or increased amounts of chemicals that stimulate the expression of osteogenic chemicals.9 With improper expression of these inhibitory or stimulatory chemicals, the calcifying vascular cells lose their normal ability to produce smooth muscle-specific chemical markers and instead become osteogenic, thereby forming calcified plaques.

Even less well understood is how short sleep durations may lead to coronary artery calcification. One possibility may be the impact that short sleep durations have on the sympathetic nervous system. Studies1 show that blood pressure rises after a night of sleep deprivation. Since hypertension is a risk factor for developing coronary calcification, it may be that short sleep durations increase calcification by the same pathophysiological route. In addition to sympathetic activation, sleep deprivation has been associated with an increased inflammatory response,3,4 which is a risk factor for developing calcium plaques.

Sleep deprivation also has metabolic effects such as decreased glucose tolerance,2 which can result in increased blood glucose levels. Increased glucose in the blood may then play a role in oxidative stress,6 thereby leading to an increased risk of developing calcium plaques.

King and colleagues appear to be the first scientists to objectively link short sleep duration with calcification. Other scientists have noted the association, but their studies used information concerning sleep duration that was based on the study participants' self-reports. Because not many objective studies yet exist, scientists do not know to what extent sleep duration moderates the rate of coronary artery calcification or to what extent sleep duration can affect the outcome of calcification or whether sleep duration can be used to predict the outcome of calcification. If future studies prove that sleep duration can impact the rate of calcification or impact the outcome of calcification, people with sleep problems that result in chronic insufficient sleep may need to be more quickly assessed and diagnosed to prevent or lessen the negative consequences of coronary artery calcification.

Regina Patrick, RPSGT, is a contributing writer for Sleep Review. She can be reached at


  1. Gangwisch JE, Heymsfield SB, Boden-Albala B, et al. Short sleep duration as a risk factor for hypertension: analyses of the first National Health and Nutrition Examination Survey. Hypertension. 2006;47(5):833839.
  2. King CR, Knutson KL, Rathouz PJ, Sidney S, Liu K, Lauderdale DS. Short sleep duration and incident coronary artery calcification. JAMA. 2008;300(24):28592866.
  3. Irwin MR, Wang M, Campomayor CO, Collado-Hidalgo A, Cole S. Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation. Arch Intern Med. 2006;166(16):17561762.
  4. Irwin MR, Wang M, Ribeiro D, et al. Sleep loss activates cellular inflammatory signaling. Biol Psychiatry. 2008;64(6):538540.
  5. Tintut Y, Patel J, Territo M, Saini T, Parhami F, Demer LL. Monocyte/macrophage regulation of vascular calcification in vitro. Circulation. 2002;105(5):650655.
  6. Guzman RJ. Clinical, cellular, and molecular aspects of arterial calcification. J Vasc Surg. 2007;45(suppl A):A57A63.
  7. Byon CH, Javed A, Dai Q, et al. Oxidative stress induces vascular calcification through modulation of the osteogenic transcription factor Runx2 by AKT signaling. J Biol Chem. 2008;283:1531915327.
  8. Tyson KL, Reynolds JL, McNair R, Zhang Q, Weissberg PL, Shanahan CM. Osteo/chondrocytic transcription factors and their target genes exhibit distinct patterns of expression in human arterial calcification. Arterioscl Thromb Vasc Biol. 2003;23(3):489494.
  9. Tintut Y, Parhami F, Bostrom K, Jackson SM, Demer LL. cAmp stimulates osteoblast-like differentiation of calcifying vascular cells. Potential signaling pathway for vascular calcification. J Biol Chem. 1998;273:75477553.
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