Atherosclerosis is chronic disease, the prevalence of which has increased steadily as the population ages. Vascular injury is believed to be critical initiating event in pathogenesis of spontaneous atherosclerosis. Syndrome of accelerated atherosclerosis has been classically described in patients undergoing heart transplantation, coronary artery bypass graft, and percutaneous transluminal coronary angioplasty. In contrast to spontaneous atherosclerosis, denuding endothelial injury followed by thrombus formation and initial predominant smooth muscle cell proliferation is believed to be playing a significant role in accelerated atherosclerosis. There is no universal definition of rapid progression of atherosclerosis. However most studies describing the phenomenon have used the following definition: (i) > or = 10% diameter reduction of at least one preexisting stenosis > or = 50%, (ii) > or = 30% diameter reduction of a preexisting stenosis <50%, and (iii) progression of a lesion to total occlusion within few months. Recent studies have described the role of coronary vasospasm, human immunodeficiency virus, various inflammatory markers, and some genetic mutations as predictors of rapid progression of atherosclerosis. As research in the field of vascular biology continues, more factors are likely to be implicated in the pathogenesis of rapid progression of atherosclerosis.
The prevalence of atherosclerosis has increased steadily due to aging population. Economic development and urbanization have promoted habits of diet rich in saturated fat and diminished physical activity, which favors atherosclerosis [
Vascular injury in the form of endothelial injury is a critical initiating event in pathogenesis of both spontaneous and accelerated atherosclerosis [
Accelerated atherosclerosis was initially described in the 1980s in patients undergoing heart transplant, CABG, and PTCA [
Coronary vein graft disease contributes to significant morbidity and mortality in post-CABG patients. About 20% vein grafts are occluded by 1 year and, at the end of 5 years, 35% vein grafts will be occluded [
After PTCA, 5% have acute reocclusion and about 35% have restenosis within 6 months [
Apart from the conditions described in accelerated atherosclerosis, coronary artery disease has been shown to progress significantly over period of months to few years in a subset of patients. Hence the term rapid progression of atherosclerosis has been used recently in the literature. Anatomical and physiological as well as inflammatory markers have been implicated in rapid progression of atherosclerosis [
Nobuyoshi et al. in 1991 [
Mechanisms by which spasm can lead to rapid progression of atherosclerosis are putative. It is believed that spasm can make the endothelium dysfunctional and can disrupt it [
A complex coronary lesion is defined as those having irregular borders, overhanging edges, and intracoronary thrombi. Angiographic studies have indicated that complex lesion morphology is associated with increased risk of myocardial infarction [
The roughness of plaque surface is believed to cause increased thrombogenicity and platelet deposition. This then leads to cascade of events similar to that in accelerated atherosclerosis. Adherence of platelets to a disrupted intima followed by the release of procoagulant metabolites and concomitant enhanced vasoreactivity may predispose to thrombotic coronary occlusion [
Zouridakis et al. evaluated 224 coronary stenoses in 92 patients with chronic stable angina for rapid progression by 2 angiograms done 5.5 (±3) months apart. The definition of rapid progression was as follows: (i) > or = 10% diameter reduction of at least one preexisting stenosis > or = 50%, (ii) > or = 30% diameter reduction of a preexisting stenosis <50%, and (iii) progression of a lesion to total occlusion. They showed that plasma endothelin levels were significantly higher in patients with rapid progression than those without. But, the use of statins was very low (41% and 28% in nonrapid and rapid progressors, resp.). However, after adjustment of multiple factors, endothelin was an independent predictor of disease progression and endothelin levels >4.26 pg/mL were associated with 6-fold increase in risk of rapid disease progression [
Endothelins are a family of potent vasoconstrictor peptides, which have cell growth-promoting and mitogenic properties. Macrophage-rich areas, hypercellular areas showing neovascularization, and areas with evidence of previous intraplaque hemorrhage were significantly associated with the presence of endothelin-1. Accelerated proliferation of vascular cells may be a contributing mechanism for rapid coronary lesion progression [
Terres et al. studied 79 patients with at least one coronary artery stenosis > or = 50%. Coronary angiography was performed at a mean of 66 (±25) days. Rapid progression was defined as follows: (i) an increase in >10% in stenosis severity in at least one stenosis > or = 50%, (ii) occurrence of new stenosis > or = 50%, or (iii) occlusion of a formerly patent vessel. They found that elevated serum Lp(a) levels were independently associated with rapid disease progression [
Lp(a) is a plasma lipoprotein composed of apolipoprotein B-100 and shares a high degree of structural homology with plasminogen. It attenuates the activation of plasminogen by streptokinase and tissue plasminogen activator and there is competition between Lp(a) and plasminogen for binding sites on endothelial cells, platelets, and fibrinogen and fibrin. Thus it exerts antifibrinolytic action. Lp(a) is also shown to stimulate the proliferation of human smooth muscle cells [
Nakachi et al. studied 153 patients with non-ST-elevation acute coronary syndrome who underwent PCI and follow-up coronary angiography in 7 months. Rapid progression was defined as follows: (i) > or = 10% diameter reduction of at least one preexisting stenosis > or = 50%, (ii) > or = 30% diameter reduction of a preexisting stenosis <50%, and (iii) progression of a lesion to total occlusion. Admission CRP elevation (odds ratio 2.92) and post-PCI (48 hours) CRP elevation (odds ratio 2.67) along with multiple complex lesions were independent predictors of rapid progression of nonculprit lesions. This study did not evaluate other inflammatory markers. Patients with conditions known to elevate CRP were excluded from the study [
Few things can explain this association. Trauma associated with diagnostic part of the procedure may trigger an inflammatory response. Rise of CRP after PCI can be attributed to inflammatory stimuli associated with plaque disruption and coronary artery injury during balloon inflation and stent implantation. Disruption of vulnerable plaque also causes microembolization, resulting in low-grade myonecrosis, which has been suggested to be the main source of inflammatory stimuli in such patients. It is believed that CRP is produced endogenously in the vessel wall or in coronary atherosclerotic plaques injured by PCI. Rapid progression of nonculprit lesions can result from negative remodeling and organization of plaque hemorrhages or from repeated subclinical cycles of rupture, hemorrhage, and organization [
Neopterin, MMP-9, and ICAM-1 were shown to independently predict rapid progression along with CRP levels in a study of 124 chronic stable angina patients [
Mazzone et al. studied 77 patients with acute coronary syndrome (ACS) and chronic angina who had coronary angiograms done 6 months apart. Baseline osteopontin levels were associated with rapid coronary plaque progression [
Osteopontin in the plaque is believed to exert its effect through upregulation within and in proximity to activated cells, thereby becoming responsible for changes leading to instability, and inducing matrix metalloproteinase release, angiogenesis, hemorrhage, fibrous cap degradation, and thrombotic complications [
A study of 123 patients with ACS who underwent PCI and follow up (mean interval of 1 year) angiography showed Lp-PLA2 to be an independent predictor of rapid progression of nonculprit coronary lesions. Rapid progression was defined as (i) > or = 10% diameter reduction of at least one preexisting stenosis > or = 50%, (ii) > or = 30% diameter reduction of a preexisting stenosis <50%, and (iii) progression of a lesion to total occlusion [
Lp-PLA2 is a novel inflammatory marker involved in bioactive lipid formation and pathogenesis of atherosclerosis. It is present in thin cap fibroatheromas and is preferentially secreted by macrophage and hydrolysed chemoattractants could contribute to development and progression of atherosclerotic lesions.
Spotty calcification is defined as presence of lesions 1–4 mm in length containing an arc of calcification <90 degrees. A total of 1347 stable patients who underwent serial evaluation with intravascular ultrasound imaging after a mean follow-up of about 650 days in 6 trials were studied. Spotty calcification was associated with greater progression of percent atheroma volume (PAV) [
Coronary artery calcification can occur via a complex, regulated process of biomineralization resembling osteogenesis. Spotty calcified plaque may contain more lipid and inflammatory materials than noncalcified lesions and therefore is likely to undergo greater atheroma progression.
Rheumatoid arthritis (RA) is associated with increased risk of cardiovascular events and the mortality is high [
No studies have evaluated the effect of chronic cocaine use in progression of atherosclerosis. However, 2 cases have been reported whereby significant progression of coronary atherosclerosis occurred in young patients (in their 30s) over a period of 9–16 months [
Syndrome of accelerated atherosclerosis had been classically described in patients after heart transplant, CABG, and PTCA. However, rapid progression of atherosclerosis seems to occur in certain other groups of patients with vasospasm, complex stenosis morphology, certain elevated inflammatory markers, spotty calcification, systemic disease like RA, and chronic cocaine use. Increased inflammation is probably the final pathway that leads to rapid progression of atherosclerosis. As far as role of inflammatory markers is concerned, most of the studies focused on one marker. So it remains to be seen if all the markers are simultaneously studied, which ones will predict the rapid progression of atherosclerosis. A recent study showed critical impairment of adaptive immune response in patients with ACS with reduced expression of regulatory T cells and enhanced effector T cell responsiveness [
The authors declare that there is no conflict of interests regarding the publication of this paper.