Coronary Atherosclerotic Phenotype and Plaque Healing in Patients With Recurrent Acute Coronary Syndromes Compared With Patients With Long-term Clinical Stability

Abstract

IMPORTANCE At one end of the coronary artery disease (CAD) spectrum, there are patients with multiple recurrent acute coronary syndromes (rACS), and at the other end there are those with long-standing clinical stability. Predicting the natural history of these patients is challenging because unstable plaques often heal without resulting in ACS. OBJECTIVE To assess in vivo the coronary atherosclerotic phenotype as well as the prevalence and characteristics of healed coronary plaques by optical coherence tomography (OCT) imaging in patients at the extremes of the CAD spectrum. DESIGN, SETTING, AND PARTICIPANTS This is an observational, single-center cohort study with prospective clinical follow-up. From a total of 823 consecutive patients enrolled in OCT Registry of the Fondazione Policlinico A. Gemelli-IRCCS, Rome, Italy, from March 2009 to February 2016, 105 patients were included in the following groups: (1) patients with rACS, defined as history of at least 3 acute myocardial infarctions (AMIs) or at least 4 ACS with at least 1 AMI; (2) patients with long-standing stable angina pectoris (ls-SAP), defined as a minimum 3-year history of stable angina; and (3) patients with a single unheralded AMI followed by a minimum 3-year period of clinical stability (sAMI). Data were analyzed from January to August 2018. EXPOSURES Intracoronary OCT imaging of nonculprit coronary segments. MAIN OUTCOMES AND MEASURES Coronary plaque features and the prevalence of healed coronary plaques in nonculprit segments as assessed by intracoronary OCT imaging. RESULTS Of 105 patients, 85 were men (81.0%); the median (interquartile range) age was 68 (63-75) years. Median (interquartile range) time of clinical stability was 9 (5.0-15.0) years in the ls-SAP group and 8 (4.5-14.5) years in the sAMI group. Patients in the rACS and sAMI groups showed similar prevalence of lipid-rich plaque and thin-cap fibroatheroma, which was significantly higher than in those with ls-SAP (lipid-rich plaque 80.0% [n = 24 of 30] vs 76.3% [n = 29 of 38] vs 37.8% [n = 14 of 37], respectively; P < .001; thin-cap fibroatheroma 40.0% [n = 12 of 30] vs 34.2% [n = 13 of 38] vs 8.1% [n = 3 of 37], respectively; P = .006). Spotty calcifications were more frequently observed in patients with rACS than in those with ls-SAP and sAMI (70.0% [n = 21 of 30] vs 40.5% [n = 15 of 37] vs 44.7% [n = 17 of 38], respectively; P = .04). Healed coronary plaques were rarely observed in patients with rACS, whereas their prevalence was significantly higher in patients with ls-SAP and sAMI (3.3% [n = 1 of 30] vs 29.7% [n = 11 of 37] vs 28.9% [n = 11 of 38], respectively; P = .01). CONCLUSIONS AND RELEVANCE Patients with rACS have a distinct atherosclerotic phenotype compared with those with ls-SAP, including higher prevalence of thin-cap fibroatheroma and lower prevalence of healed coronary plaques, suggesting that atherosclerotic profile and plaque healing may play a role in leading the natural history of patients with CAD.

How to prevent cardiovascular events from recurring

“…This healthy user bias is a confounder and difficult to quantify, but has to be considered when interpreting the evidence presented by Lassenius et al Interestingly, upon stratification by sex (as depicted in the Cox model of recurrent events in Table 3), levels of LDL-C were no longer significantly associated with event recurrence in males. 4 While this may be attributable to a loss of power caused by the splitting of the groups, these data align with data by Vergallo et al, 6 where the expression of markers of atherogenic dyslipidaemia, but not LDL-C, discriminated between patients with multiple recurrent acute coronary syndromes and long-standing clinical stability, as outlined in further detail below. 7,8 Taken together, Lassenius et al showed in a large cohort representing real life that a substantial number of patients did not reach their LDL-C goal and that statin adherence decreased over time.…”

“…11 The lipoprotein pattern referred to as atherogenic dyslipidaemia is a prominent lipid trait associated with metabolic syndrome and ASCVD. 12 Interestingly, in a recent study by Vergallo et al, 6 neither LDL-C level nor statin use discriminated between patients with multiple recurrent acute coronary syndromes and long-standing clinical stability. 7 Conversely, global inflammatory burden (hsCRP levels) and the expression of atherogenic dyslipidaemia were higher in the recurrent acute coronary syndrome group compared with the long-standing stable angina group, with high-density lipoprotein cholesterol (HDL-C) levels showing statistical significance.…”

High-Risk Atherosclerosis and Metabolic Phenotype: The Roles of Ectopic Adiposity, Atherogenic Dyslipidemia, and Inflammation

“…61 Furthermore, the TG/HDL-C ratio has been linked to plaque phenotype and clinical stability in coronary artery disease: the ratio was significantly higher in patients with TCFAs than in those without, and it was nonsignificantly higher in patients with multiple recurrent acute coronary syndromes than in those with long-standing stable angina. [82][83][84] Of note, triglycerides and the TG/HDL-C ratio do not reliably predict insulin resistance in African Americans. This has been linked to the observation that insulin resistance does not impair lipoprotein lipase in this subgroup and thus does not induce hypertriglyceridemia.…”

Intravascular Polarimetry: Clinical Translation and Future Applications of Catheter-Based Polarization Sensitive Optical Frequency Domain Imaging

“…In a recent ex vivo study investigating the accuracy of OCT for diagnosing healed ruptured plaques, Shimokado et al proposed the presence of layered structures in the conventional OCT intensity signal as a predictor of histologically determined healed ruptures of coronary plaques (75). Furthermore, clinical studies have demonstrated that layered structure in superficial plaques identified by OCT are associated with plaque vulnerability or rapid progression of coronary artery stenosis (10,76), although there remains some controversy and another study found similar features to indicate enhanced plaque stability (23). Despite the importance of assessing the healing process of coronary thrombus, the conventional OCT intensity image provides limited insight into the process of thrombus organization.…”

“…Also, it is now a well-accepted concept that plaque rupture and erosion frequently occur silently without causing clinical symptoms, emphasizing the crucial role of vascular healing in determining the fate of a lesion (1,21). Therefore, the mechanisms that impair vascular healing are increasingly investigated to explain disease progression and the development of ACS (22)(23)(24). Following stent implantation, vascular healing and tissue response play a similar decisive role in defining the risk of stent failure and future complications (25)(26)(27)(28).…”