The role of serial carotid intima-media thickness assessment as a surrogate marker of atherosclerosis control in patients with recent myocardial infarction

Introduction: Despite percutaneous coronary intervention (PCI), patients after their first myocardial infarction (MI) are at high risk of ischemic event recurrence. Therefore, there is a need for objective markers of adequate atherosclerosis control, independent of prescribed pharmacotherapy and patients’ compliance. Such a potential indicator of major adverse cerebral and coronary event (MACCE) risk might be change in carotid intima-media thickness (CIMT), which indicates atherosclerosis growth. Aim: To evaluate the potential associations between CIMT changes and the incidence of MACCE and recurrent MI. Material and methods: The CIMT assessments at baseline and during 2 follow-up visits were performed in 215 patients admitted with MI, in whom PCI was performed for an index lesion, followed by best medical treatment. The incidences of MACCE (cardiovascular death, recurrent MI, ischemic stroke) and new onset angina were recorded prospectively. Results: The MACCE were recorded in 65 (30.2%) patients and angina due to coronary lesion progression (CLP) in 27 (12.5%) patients. Although initial CIMT values were similar in patients who suffered MACCE vs. MACCE-free patients (1.43 ±0.40 vs. 1.45 ±0.44 mm; p = 0.486), patients in whom MACCE occurred had greater annual CIMT growth as assessed at the first (0.024 ±0.12 vs. 0.009 ±0.16 mm/year; p 0.003 mm/year (sensitivity: 84.5%, specificity: 49.3%) for MI plus CLP (AUC = 0.673) occurred an independent indicator of MACCE (HR = 3.00; 95% CI: 1.496–6.016), recurrent MI (HR = 4.59, 95% CI: 1.591–13.217), and MI plus CLP (HR = 3.50, 95% CI: 1.759–6.964). Conclusions: Annual CIMT change might be a potentially valuable marker of atherosclerosis response to post-MI treatment

Prospective study on the prognostic value of repeated carotid intima-media thickness assessment in patients with coronary and extra coronary steno-occlusive arterial disease

It is debatable whether the rate of change in carotid intima‑media thickness (CIMT) may be used as a risk indicator of major adverse cerebral and coronary events (MACCEs) in patients with either coronary (CAD) and peripheral artery disease (PAD). This prospective study aimed to evaluate the association between CIMT changes and the incidence of MACCEs, in patients with symptomatic CAD and PAD. The study comprised 466 patients admitted with steno‑occlusive disease, in whom revascularization was performed for an index lesion. Group 1 included 305 subjects with CAD, and group 2, 161 patients with PAD. CIMT was measured at baseline and at a median of 21 and 41 months afterwards. The incidence of MACCE, cardiovascular death (CVD), myocardial infarction (MI), and ischemic stroke was recorded prospectively during 5 years. CIMT increased with a mean (SD) progression rate of 0.027 (0.16) mm/y in group 1 and 0.026 (0.17) mm/y in group 2 (P = 0.89). CIMT regression was recorded in 112 patients (36.7%) and 61 patients (37.9%) in groups 1 and 2, respectively, at baseline (P = 0.80), and 82 patients (26.9%) and 42 patients (26.1%) in groups 1 and 2, respectively, in follow‑up (P = 0.85). Maintained CIMT regression was independently associated with a reduced risk of MACCEs (hazard ratio [HR], 0.25, 95% CI, 0.15-0.42), MI (HR, 0.32; 95% CI, 0.20-0.51), ischemic stroke (HR, 0.29; 95% CI, 0.18-0.45), and CVD (HR, 0.24; 95% CI, 0.15-0.40), while the CIMT progression rate of 0.056 mm/y was associated with an increased risk of MACCEs (sensitivity, 53.2%; specificity, 72.2%; area under the receiver operating curve, 0.65). Maintained CIMT regression is associated with 68% to 75% reduction in the risk of a cardiovascular event. However, a long‑term maintained CIMT regression is achieved in one‑fourth of patients with either CAD or PAD

Diagnostyczne i prognostyczne micro-RNA u pacjentów z udarem niedokrwiennym mózgu w przebiegu objawowego zwężenia tętnicy szyjnej wewnętrznej oraz u pacjentów z ostrym zespołem wieńcowym: 4-letnie badanie prospektywne

Background: Circulating microRNAs (miRs) levels are potentially important diagnostic and prognostic biomarkers in acute coronary syndrome (ACS) or cerebral ischaemic events (CIE) resulting from internal carotid artery stenosis (ICAS). Aim: This four-year prospective study aimed to compare the levels of circulating miRs in ACS vs. CIE patients, and investigate miRs potentially associated with risk of recurrent cardiovascular events. Methods: The circulating miRs levels (miR-1-3p, miR-16-5p, miR-34a-5p, mir-122-5p, miR-124-3p, miR-133a-3p, miR-133b, miR-134-5p, miR-208b-3p, miR-375, and miR-499-5p) were compared in 43 (34 men, 57.6 ± 10.1 years) patients with ACS, and in 71 (47 men, 69.5 ± 9.6 years) with CIE due to ICAS. A four-year prospective evaluation of miRs associated with risk of cardiovascular death (CVD), myocardial infarction (MI), CIE, or all (CVD/MI/CIE) was performed. Results: In ACS vs. CIE patients, the levels of miR-124-3p (p &lt; 0.001), miR-134-5p (p = 0.012), miR-208b-3p (p &lt; 0.001), miR-34a-5p (p &lt; 0.001), and miR-499-5p (p &lt; 0.001) were higher, while levels of miR-16-5p (p &lt; 0.001) and miR-122-5p (p &lt; 0.001) were lower. Levels of miR-1-3p (p = 0.195), miR-133a-3p (p = 0.333), miR-133b (p = 0.056), and miR-375 (p = 0.055) were non-statistically different. During follow-up (median 57 months, Q1–Q3: 54–60), CVD/MI/CIE occurred in 23 subjects, including eight CVDs, five non-fatal CIEs, and 10 non-fatal MIs. The multivariate Cox proportional hazard analysis (relative risk [RR]; 95% confidence interval [CI]) revealed that miR-208b-3p (1.225; 1.092–1.375), miR-34a-5p (0.963; 0.935–0.992), and miR-499-5p (0.077; 0.025–0.239) were independently associated with risk of CVD/MI/CIE, as well as risk of each event. Furthermore, miR-133b (1.009; 1.003–1.015) was associated with risk of CVD. Conclusions: This study shows that although most investigated miRs levels differ significantly between patients with ACS and CIE, similar levels of circulating miR-1-3p, miR-133a-3p, miR-133b, and miR-375 were observed; furthermore, we identified several common miRs as possible risk factors for recurrent cardiovascular events.Wstęp: Wydaje się że, osoczowe microRNA (miRs) mogą mieć istotną wartość kliniczną w ostrych zespołach wieńcowych (ACS) oraz niedokrwiennych incydentach mózgowych (CIE), zależnych od miażdżycowego zwężania tętnicy szyjnej wewnętrznej zarówno w diagnostyce, jak w prospektywnej ocenie ryzyka zdarzeń sercowo-naczyniowych (CVE). Cel: Celem badania było porównanie ekspresji osoczowych miRs u chorych z miażdżycowym zwężeniem tętnicy wieńcowej w przebiegu troponino-dodatniego ACS i objawowym zwężeniem tętnicy szyjnej wewnętrznej oraz próba identyfikacji miRs niezależnie związanych z ryzykiem CVE. Metody: Stężenie osoczowych miRs (miR-1-3p, miR-16-5p, miR-34a-5p, mir-122-5p, miR-124-3p, miR-133a-3p, miR-133b, miR-134-5p, miR-208b-3p, miR-375 i miR-499-5p) zostały przeanalizowane w grupie 43 pacjentów z ACS (34 mężczyzn; 57,6 ± 10,1 roku) i 71 pacjentów z CIE (47 mężczyzn, 69,5 ± 9,6 roku). W 4-letniej prospektywnej obserwacji podjęto próbę identyfikacji miRs związanych z ryzykiem CVE: zgonu sercowo-naczyniowego (CVD), zawału serca (M), CIE oraz złożonego punktu końcowego (CVD/MI/CIE) za pomocą wieloczynnikowej analizy hazardu proporcjonalnego metodą Coxa. Wyniki: W grupie ACS stwierdzono istotnie wyższe stężenia miR-124-3p (log 2–ΔCt 0.571 ± 0,07 vs. –0,638 ± 0,06; p < 0,001), miR-134-5p (log 2–ΔCt 0,278 ± 0,09 vs. –0,02 ± 0,07; p = 0,012), miR-208b-3p (log 2–ΔCt –0,899 ± 0.08 vs. –1,998 ± 0,149; p < 0,001), miR-34a-5p (log 2–ΔCt 0,238 ± 0.08 vs. –0,248 ± 0,07; p < 0,001), i miR-499-5p (log 2–ΔCt –0,899 ± 0,08 vs. –1,176 ± 0,07; p < 0,001), a mniejsze stężenie miR-16-5p (log 2–ΔCt -–0,072 ± 0,08 vs. 1,962 ± 0,103; p < 0,001) i miR-122-5p (log 2–ΔCt –0,076 ± 0,08 vs. 1,892 ± 0,09; p < 0,001) w porównaniu z pacjentami z CIE. Nie stwierdzono istotnej statystycznie różnicy w stężeniu miR-1-3p (p = 0,195), miR-133a-3p (p = 0,333), miR-133b (p = 0,056) i miR-375 (p = 0,055). Obserwacje odległą uzyskano dla 112 (98,2%) chorych. W trakcie 4-letniej obserwacji incydenty CVD/MI/CIE stwierdzono u 23 (20,5%) chorych. Wieloczynnikowa analiza Coxa (RR; 95% CI) wykazała, że niezależnymi czynnikami ryzyka CVE, jak również CVD, MI, CIE są: miR-208b-3p (1,225; 1,092–1,375), miR-34a-5p (0,963; 0,935–0,992), miR-499-5p (0,077; 0,025–0,239). Ponadto miR-133b (1,009; 1,003–1,015) było związane z ryzykiem wystąpienia CVD. Wnioski: Stężenie wybranych osoczowych miRs w miażdżycowym objawowym zwężeniu tętnicy szyjnej wewnętrznej oraz u chorych z ACS różnią się istotnie, z wyjątkiem stężenia miR-1-3p, miR-133a-3p, miR-133b, and miR-375, co mogłoby wskazywać na wspólną etiologię miażdżycową ich ekspresji. Ponadto miR-208b-3p, miR-34a-5p, miR-499-5p oraz miR-133b wydają się być istotnie związane z ryzykiem CVE w obserwacji prospektywnej

Decyzyjne mikroRNA (miR-124, -133a/b, -34a i -134) u pacjentów z zamkniętym naczyniem odpowiedzialnym za zawał z ostrym zespołem wieńcowym

Background: Coronary artery occlusion does not always manifest with ST-elevation, and some patients can have patent coronary vessel. Aim: We evaluated circulating microRNA (miRNA) profiles to discriminate subjects with infarct-related artery (IRA) occlusion. Methods and results: Patients (n = 43) with uncomplicated acute coronary syndrome and positive troponins were classified with respect to patent vs. occluded IRA or ST-elevation vs. non-ST elevation MI (STEMI vs. NSTEMI). Expression levels of serum miRNAs (miR-1, -16, -34a, -122, -124, -208b, -133a/b, -375, and -499) were analysed. Out of 16 STEMI and 27 NSTEMI patients, IRA occlusion was noted in 12 and 15 patients, respectively. The remaining four STEMI and 12 NSTEMI patients had patent IRA. STEMI patients had higher troponin T levels and a 3.83-fold higher miR-134 expression (p &lt; 0.025). Patients with the occluded vs. patent IRA had higher levels of miR-133a (fold change: 7.00), miR-133b (4.57), miR-34a (5.50), miR-124 (2.55), and miR-134 (3.45) but no difference in troponin T levels. Receiver operator characteristic analysis identified decision-making miRNAs in occluded vessels: miR-124 (AUC: 0.787, p &lt; 0.001), miR-133b (AUC: 0.704, p = 0.006), and miR-134 (AUC: 0.686, p = 0.016). With respect to STEMI, only miR-134 showed a discriminating value (AUC: 0.725, p = 0.002). Conclusions: The degree of IRA occlusion determines circulating miRNA expression, and specific miRNAs may be useful in indicating patients requiring urgent coronary revascularisation.Wstęp: Zamknięcie tętnicy wieńcowej nie zawsze manifestuje się uniesieniem odcinka ST w elektrokardiogramie, a zawał serca z uniesieniem odcinka ST (STEMI) nie jest równoznaczny z zamkniętą tętnicą odpowiedzialną za zawał (IRA). Cel: Celem pracy była ocena profilu krążących mikroRNA (miRNA), które różnicują pacjentów z zamkniętą IRA. Metody i wyniki: Pacjenci (n = 43) z niepowikłanym troponino-dodatnim ostrym zespołem wieńcowym podzielono na grupy z drożną vs. zamkniętą IRA oraz z zawałem serca z uniesieniem odcinka ST vs. bez uniesienia odcinka ST (STEMI vs. NSTEMI). W surowicy analizowano poziomy ekspresji następujących miRNA: miR-1, -16 -34a, -122, -124, -208b, -133a/b, -375 i -499. Spośród 16 pacjentów ze STEMI i 27 z NSTEMI okluzje IRA stwierdzono odpowiednio u 12 i 15 pacjentów. U pozostałych 4 chorych z STEMI i 12 z NSTEMI stwierdzono drożną IRA. W grupie STEMI stwierdzono wyższe stężenie troponiny T i 3,83-krotnie większą ekspresję miR-134 (p &lt; 0,025). W grupie z niedrożną vs. drożną IRA stwierdzono wyż­szy poziom miR-133a (krotność zmian: 7,00), miR-133b (4,57), miR-34a (5,50), miR-124 (2,55) i miR-134 (3.45), ale nie odnotowano różnicy stężeń troponiny T. Za pomocą krzywej ROC zidentyfikowano decyzyjne miRNA zamkniętej IRA: miR 124 (AUC: 0,787; p &lt; 0,001), miR-133b (AUC: 0,704; p = 0,006) i miR-134 (AUC: 0,686; p = 0,016). W grupie STEMI tylko miR‑134 wykazało wartość różnicującą (AUC: 0,725; p = 0,002). Wnioski: Stopień zwężenia IRA określa poziom ekspresji krążących miRNA, a specyficzne miRNA mogą być użyteczne w podjęciu decyzji o pilnej rewaskularyzacji wieńcowej

Circulating miRNA levels differ with respect to carotid plaque characteristics and symptom occurrence in patients with carotid artery stenosis and provide information on future cardiovascular events

Introduction: Circulating microRNAs (miRNAs) levels are potentially important biomarkers and therapeutic targets of cerebral ischemic event (CIE) in patients with internal carotid artery stenosis (ICAS). Aim: This prospective study investigated associations between circulating miRNAs and symptomatic and asymptomatic ICAS, carotid plaque morphology and future cardiovascular events. Material and methods: Circulating miRNAs (miR-1-3p, miR-16-5p, miR-34a-5p, miR-124-3p, miR-133a-3p, miR-133b, miR-134-5p, miR-208b-3p, miR-375 and miR-499-5p) were analyzed in 92 consecutive patients with significant ICAS referred for revascularization. Group I comprised 65 subjects (41 males, age 69.3 ±9.7 years) with a recent CIE. Group II comprised 27 patients (15 males, age 68.2 ±8.4 years) with asymptomatic ICAS. The ICAS degree and plaque morphology was assessed by ultrasonography. The incidences of cardiovascular death (CVD), myocardial infarction (MI) and recurrent CIE (CVD/MI/CIE) were recorded prospectively (mean: 38.7 ±3.8 months). Results: Groups II and I differed significantly in levels of miR-124-3p (p = 0.036), miR-133a-3p (p = 0.043) and miR-134-5p (p = 0.02). Hypoechogenic, as compared to echogenic, plaques differed in levels of miR-124-3p (p = 0.038), miR-34a-5p (p = 0.006), miR-133b (p = 0.048), miR-134-5p (p = 0.045), and miR-375 (p = 0.016), while calcified plaques differed in miR-16-5p (p = 0.023). Ulcerated plaques showed higher levels of miR-1-3p (p = 0.04) and miR-16-5p (p = 0.003), while thrombotic plaques showed lower levels of miR-1-3p (p = 0.032). CVD/MI/CIE occurred in 14 (15.5%) out of 90 follow-up patients. Multivariate Cox and ROC analysis showed associations between miR-1-3p and CVD (AUC = 0.634; HR = 4.84; 95% CI: 1.62–14.5; p = 0.005), MI (AUC = 0.743; HR = 7.8; 95% CI: 2.01–30.0; p = 0.003), and CVD/MI/CIE (AUC = 0.560; HR = 4.6; 95% CI: 1.61–13.1; p = 0.004), while miR-133b was associated with recurrent CIE (AUC = 0.581; HR = 2.25; 95% CI: 1.01 5.02; p = 0.047). Conclusions: A significant difference in levels of selected miRNAs is observed in symptomatic vs. asymptomatic ICAS. Plaque morphology and structure is associated with change of miRNA levels. The expression of miR-1-3p may be a potential prognostic factor for future cardiovascular events