It is now recognized that plaques responsible for myocardial infarctions and other acute coronary syndromes often are asymptomatic before the acute event; symptoms are triggered by thrombosis on a lesion that previously did not produce significant luminal occlusion. The worrisome conclusion is that large numbers of asymptomatic individuals are at risk for a catastrophic coronary event. The causes of acute plaque change are complex and include both intrinsic factors (e.g., plaque structure and composition) and extrinsic factors (e.g., blood pressure). These factors combine to weaken the integrity of the plaque, making it unable to withstand vascular shear forces.
Certain types of plaques are believed to be at particularly high risk of rupturing. These include plaques that contain large numbers of foam cells and abundant extracellular lipid, plaques that have thin fibrous caps containing few SMCs, and plaques that contain clusters of inflammatory cells. Plaques at high risk for rupture are referred to as vulnerable plaques (
Fig. 10.16 ). The fibrous cap also undergoes continuous remodeling; its mechanical strength and stability are proportional to its collagen content, so the balance of collagen synthesis and degradation affects cap integrity. Collagen in atherosclerotic plaques is synthesized primarily by SMCs, and loss of SMCs understandably results in cap weakening.
In general, plaque inflammation increases collagen degradation and reduces collagen synthesis, thereby destabilizing the mechanical integrity of the cap. Of interest, statins may have a beneficial effect not only by
Fig. 10.16 Vulnerableandstableatheroscleroticplaque.Stableplaqueshavedenselycollagenizedandthickenedfibrouscapswithminimalinflammationandnegligibleunderlyingatheromatouscores,whereasvulnerableplaqueshavethinfibrouscaps,largelipidcores,andincreasedinflammation.(Adapted from Libby P: Molecular bases of the acute coronary syndromes, Circulation91:2844, 1995.) http://ebooksmedicine.net reducing circulating cholesterol levels but also by stabilizing plaques through a reduction in plaque inflammation.
Factors extrinsic to plaques also are important. Thus, adrenergic stimulation (as with intense emotions) can increase systemic blood pressure or induce local vasoconstriction, thereby increasing the mechanical stress on a given plaque. Indeed, one explanation for the pronounced circadian periodicity in the onset of heart attacks (peak incidence between 6 AM and 12 noon) is the adrenergic surge associated with waking and rising—sufficient to cause blood pressure spikes and heightened platelet reactivity.
Fortunately, not all plaque ruptures result in occlusive thromboses with catastrophic consequences. In fact, silent plaque disruption and ensuing superficial platelet aggregation and thrombosis probably occur frequently and repeatedly in those with atherosclerosis. Healing of these subclinical plaque disruptions—and their overlying thromboses—is an important mechanism of atheroma enlargement.
Atherosclerosisisanintima-basedlesioncomposedofafibrouscapandanatheromatous(literally,“gruel-like”)core;theconstituentsoftheplaqueincludeSMCs,ECM,inflammatorycells,lipids,andnecroticdebris.
Atherogenesisisdrivenbyaninterplayofvesselwallinjuryandinflammation.ThemultipleriskfactorsforatherosclerosisallcauseECdysfunctionandinfluenceSMCrecruitmentandstimulation.
Majormodifiableriskfactorsforatherosclerosisarehypercholesterolemia,hypertension,cigarettesmoking,anddiabetesmellitus.