Persistent Myocardial Production of Follistatin-like 1 Is Associated With Left Ventricular Adverse Remodeling in Patients With Myocardial Infarction: Myocardial production of FSTL1 in AMI patients.

BACKGROUND: Although animal studies showed that Follistatin-like 1 (FSTL1) exerts cardioprotective effects against ischemic injury, little is known in humans. We examined whether FSTL1 is secreted in an infarcted myocardium and whether its production is associated with left ventricular (LV) remodeling in survivors of acute myocardial infarction. METHODS AND RESULTS: FSTL1 levels were measured by enzyme-linked immunosorbent assay in plasma collected from the aortic root and the anterior interventricular vein in 93 patients with anterior acute myocardial infarction. Measurement of FSTL1 levels and left ventriculography were repeated during the early phase (2 weeks) and the chronic phase (6 months) after MI. A persistent increment in FSTL1 levels from the aortic root to the anterior interventricular vein, reflecting FSTL1 production in the infarcted myocardium at both the early and chronic phases, was seen in 22 patients (24%). A linear regression analysis revealed that a persistent transmyocardial increment in FSTL1 levels was significantly associated with percent changes in LV end-diastolic volume index, LV end-systolic volume index, and LV ejection fraction from the early to the chronic phase (r = 0.44, 0.51, and -0.43, respectively, all P < .001). CONCLUSIONS: The persistent production of FSTL1 in the infarcted myocardium was associated with adverse LV remodeling in survivors of acute myocardial infarction.

High levels of stromal cell-derived factor-1α predict short-term progression of renal dysfunction in patients with coronary artery disease.

BACKGROUND: Stromal cell-derived factor-1α (SDF-1α) is an inflammatory chemokine that plays a critical role in cardiovascular disease. Although persistent inflammation causes renal dysfunction, it remains unclear whether SDF-1α is related to progression of chronic kidney disease. This study examined whether high levels of SDF-1α are associated with future declines in renal function in patients with coronary artery disease (CAD). METHODS: Plasma levels of SDF-1α in the peripheral blood were measured by enzyme-linked immunosorbent assay in 344 patients with CAD. All patients were followed for 24 months or until the occurrence of renal dysfunction, defined as ≥ 25% decrease in estimated glomerular filtration rate (eGFR) from baseline. RESULTS: During the follow-up period, 36 patients developed renal dysfunction. Multivariate logistic regression analysis showed that high plasma levels of SDF-1α were significantly associated with progression of renal dysfunction (odds ratio 1.65; 95% confidence intervals 1.07-2.35, p = 0.03). In addition, high plasma levels of SDF-1α had a significant incremental effect on the predictive value of known risk factors for renal dysfunction in analyses using net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI 0.58 [0.07-1.02], p < 0.01; and IDI 0.030 [0.001-0.085], p = 0.02). CONCLUSION: High plasma levels of SDF-1α were associated with the short-term decline of eGFR in patients with CAD. Thus, SDF-1α may be useful for predicting the progression of renal dysfunction in patients with CAD.

Pulmonary Vascular Resistance Is Associated With Brachial-Ankle Pulse-Wave Velocity and Adverse Clinical Outcomes in Patients With Heart Failure With Preserved Ejection Fraction.

BACKGROUND: The precise mechanisms underlying the high prevalence of pulmonary hypertension (PH) with increased pulmonary vascular resistance (PVR) in heart failure with preserved ejection fraction (HFpEF) remain largely unknown. Measurements of brachial-ankle pulse wave velocity (baPWV) have been shown to be useful for risk assessment in HF patients. Thus, this study sought to define the association of PVR with baPWV and clinical outcomes in HFpEF. METHODS AND RESULTS: Patients with HFpEF (n = 198) had measurements of baPWV and PVR by right heart catheterization, and were prospectively followed-up for <96 months or until the occurrence of a composite of all-cause death, hospitalization with worsening HF, and nonfatal acute coronary syndrome. RESULTS: Multivariate logistic analysis showed that baPWV was independently associated with PH with increased PVR (P < .001). During the follow-up period, 46 clinical events occurred. Multivariate Cox proportional hazards analysis showed that PH with increased PVR was a significant predictor of adverse outcomes after adjustment for conventional risk factors (HR 1.96, 95% CI 1.03-3.76, P = .04). CONCLUSIONS: PH with increased PVR was associated with increased baPWV and adverse clinical outcomes in HFpEF. Thus, increased arterial stiffness may contribute to increased risk predictability of PVR for patients with HFpEF.

Effect of coronary artery spasm on long-term outcomes in survivors of acute myocardial infarction.

BACKGROUND: The prevalence of coronary artery spasm (CAS) inducible by intracoronary injection of acetylcholine (ACh) is high in survivors of acute myocardial infarction (AMI). Although there is a potential risk of sudden cardiac death in patients with CAS, the prognostic value of CAS was not clear. Thus, this study examined the effect of CAS on long-term prognosis in survivors of AMI in a prospective manner. METHODS: The study included a total of 437 patients with AMI who underwent a CAS provocation test using ACh. All patients were followed prospectively for 5years or until the occurrence of the primary composite endpoint that consisted of cardiac death and acute coronary syndrome (ACS). RESULTS: CAS was induced in 195 (45%) of the study patients. During the follow-up period, 30 patients had a recurrent event (4 had cardiac death and 26 had ACS). Kaplan-Meier estimates in time-to-first-event analysis demonstrated a similar probability of the primary endpoint in patients with and without inducible CAS (p=0.13, log-rank test). The rate of each component of the composite endpoint was also comparable between the 2 patient groups. In Cox proportional hazards risk analysis, treatment with calcium channel blockers (CCBs) negatively predicted the primary endpoints in patients with inducible CAS (HR, 0.21; 95% CI, 0.08-0.55, p<0.01). CONCLUSIONS: The presence of inducible CAS did not increase the incidence of the cardiac events in AMI survivors. Treatment with CCBs may improve outcomes in AMI survivors with inducible CAS. CLINICAL TRIAL REGISTRATION: URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000021340, unique identifier: UMIN000018432.

Glycemic variability is associated with myocardial damage in nondiabetic patients with ST-elevation myocardial infarction.

BACKGROUND: Glycemic variability (GV) induces coronary microcirculatory disturbance and myocardial damage in diabetic patients with acute myocardial infarction. However, in nondiabetic acute myocardial infarction patients, the relationship between GV and myocardial damage remains unclear. PATIENTS AND METHODS: We investigated GV with a continuous glucose monitoring system in nondiabetic ST-segment elevation myocardial infarction patients treated with emergent percutaneous coronary intervention. GV was expressed as the mean amplitude of glycemic excursions (MAGE). Myocardial damage was estimated by myocardial blush grade and ST-segment resolution (STRes). STRes was defined as complete (>70%), partial (30-70%), or none (<30%). RESULTS: Consecutive patients (n=73) were enrolled and classified into a lower or higher MAGE group on the basis of the median MAGE. The higher MAGE group showed lower levels of myocardial blush grade (2.41±0.76 vs. 1.72±0.85, P=0.001) and STRes (complete: 56.8 vs. 33.3%, P=0.044; partial: 32.4 vs. 36.1%, P=0.741; none: 10.8 vs. 30.6%, P=0.037). CONCLUSION: GV was associated with myocardial damage after percutaneous coronary intervention in nondiabetic ST-segment elevation myocardial infarction patients.

Assessment of carotid plaque neovascularization using quantitative analysis of contrast-enhanced ultrasound imaging is useful for risk stratification in patients with coronary artery disease.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) of the carotid artery is a potential technique for imaging plaque neovascularization, a feature of unstable atherosclerotic plaques. This study examined whether assessment of intra-plaque neovascularization of the carotid artery using CEUS provides prognostic information in patients with coronary artery disease (CAD). METHODS: A total of 206 patients with stable CAD underwent a CEUS examination of the carotid artery and were followed up prospectively for <38 months or until a cardiac event (cardiac death, non-fatal myocardial infarction (MI), unstable angina pectoris (uAP) requiring unplanned coronary revascularization, or heart failure requiring hospitalization). The degree of contrast signals measured within the carotid plaque was quantified by calculating the mean gray scale level within the region of interest of the carotid plaque, expressed as plaque enhanced intensity. RESULTS: During the follow-up period, 31 events occurred (2 cardiac deaths, 7 non-fatal MIs, 16 uAP, and 6 heart failure). Multivariate Cox proportional hazard analysis showed that plaque enhanced intensity was a significant predictor of cardiac events independent of traditional risk factors (HR, 1.13; 95% CI, 1.05-1.21; p<0.001). The addition of the plaque enhanced intensity to traditional risk factors resulted in net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI 0.62, p=0.001; and IDI 0.106, p=0.002). CONCLUSIONS: The assessment of carotid plaque neovascularization using quantitative analysis of CEUS may be useful for risk stratification in patients with CAD.

Contrast-enhanced ultrasound imaging of carotid plaque neovascularization is useful for identifying high-risk patients with coronary artery disease.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) in the carotid artery has potential as a technique for imaging plaque neovascularization. This study examined whether CEUS could provide information on the severity and instability of coronary artery disease (CAD). METHODS AND RESULTS: A total of 304 patients with CAD and carotid plaque underwent CEUS examination of the carotid artery. Intraplaque neovascularization was identified on the basis of microbubbles within the plaque and graded as: G0, not visible; G1, moderate; or G2, extensive microbubbles. The complexity and extent of the coronary lesions were assessed angiographically. A higher grade of CEUS-assessed plaque neovascularization of the carotid artery was associated significantly with greater complexity (ρ=0.48 by Spearman's rank correlation test) and extent (ρ=0.51) of coronary lesions. G2 plaque neovascularization was a risk for acute coronary syndrome, independent of traditional risk factors (odds ratio 1.91, 95% confidence interval 1.04-3.53, P<0.01). Subgroup analysis showed that carotid CEUS-assessed neovascularization regressed in 12 (46%) of 26 plaques in patients during 6 months of statin treatment, whereas regression occurred in 2 (14%) of 14 plaques in patients not taking a statin (P=0.04, Chi-square test). CONCLUSIONS: CEUS examination of the carotid artery may provide valuable information on the severity and instability of CAD and also the efficacy of antiatherosclerotic treatment.

Short-term progression of maximum intima-media thickness of carotid plaque is associated with future coronary events in patients with coronary artery disease.

OBJECTIVE: This study examined whether changes in maximum intima-media thickness of carotid plaque (plaque-IMTmax) over 6 months predict future coronary events in patients with carotid plaque and coronary artery disease (CAD). METHODS: This study included 240 patients with CAD who had a carotid plaque (IMT ≥ 1.1mm) at entry. A carotid ultrasound examination was performed at entry (1st test) and after 6 months (2nd test). The carotid plaque with the greatest axial thickness at the 1st test was selected as the target plaque for monitoring the change in plaque-IMTmax. After the 2nd test, patients were prospectively followed-up for 3 years or until the occurrence of one of the following coronary events: cardiac death, non-fatal myocardial infarction, or unstable angina pectoris requiring coronary revascularization. RESULTS: The change in plaque-IMTmax over 6 months ranged from -0.85 to 0.97 mm (mean, -0.006 ± 0.319 mm). There were 41 events during follow-up. In a stepwise multivariate Cox proportional hazards model, the change in plaque-IMTmax was a significant predictor of coronary events after adjustment for known risk factors (HR per 0.1mm increase over 6 months, 1.21; 95%CI, 1.10-1.33, p=0.0001). Analysis of receiver operating characteristic (ROC) curves showed that the addition of the change in plaque-IMTmax to conventional risk factors resulted in a greater area under the ROC curve compared with conventional risk factors alone (0.81 and 0.70, respectively, p=0.02). CONCLUSION: Short-term progression of carotid plaque-IMTmax was associated with future coronary events in patients with CAD.