Quantitative Flow Ratio-Derived Index of Microcirculatory Resistance as a Novel Tool to Identify Microcirculatory Function in Patients with Ischemia and No Obstructive Coronary Artery Disease.

BACKGROUND: Coronary microvascular disease (CMVD) is associated with adverse cardiovascular outcomes. However, there is no reliable and noninvasive quantitative diagnostic method available for CMVD. The use of a pressure wire to measure the index of microcirculatory resistance (IMR) is possible, but it has inevitable practical restrictions. We hypothesized that computation of the quantitative flow ratio could be used to predict CMVD with symptoms of ischemia and no obstructive coronary artery disease (INOCA). METHODS: We retrospectively assessed the diagnostic efficiency of the quantitative flow ratio-derived index of microcirculatory resistance (QMR) in 103 vessels from 66 patients and compared it with invasive IMR using the thermodilution technique. RESULTS: Patients were divided into the CMVD group (41/66, 62.1%) and non-CMVD group (25/66, 37.9%). Pressure wire IMR measurements were made in 103 coronary vessels, including 44 left descending arteries, 18 left circumflex arteries, and 41 right coronary arteries. ROC curve analysis showed a good diagnostic performance of QMR for all arteries (area under the curve = 0.820, 95% confidence interval 0.736-0.904, p < 0.001) in predicting microcirculatory function. The optimal cut-off for QMR to predict microcirculatory function was 266 (sensitivity: 82.9%, specificity: 72.6%, and diagnostic accuracy: 76.7%). CONCLUSION: QMR is a promising tool for the assessment of coronary microcirculation. The assessment of the IMR without the use of a pressure wire may enable more rapid, convenient, and cost-effective assessment of coronary microvascular function.

The correlation between lipoprotein(a) elevations and the risk of recurrent cardiovascular events in CAD patients with different LDL-C levels.

BACKGROUND: Lipoprotein(a) [Lp(a)] elevation is an important risk factor for coronary artery disease (CAD). However, the correlation between Lp(a) elevations and the risk of recurrent cardiovascular events in patients with established cardiovascular disease is controversial. Some studies have shown that Low-density lipoprotein cholesterol (LDL-C) levels may influence the association between Lp(a) and cardiovascular risk. Our study aims to explore the correlation between Lp(a) elevations and cardiovascular risk in patients with different LDL-C levels. METHODS: We included 516 patients who received coronary stents due to acute coronary syndrome (ACS) and followed them for three years. They were divided into low-Lp(a) group and high-Lp(a) group according to Lp(a) levels, and the incidence of major adverse cardiovascular events (MACE) and acute coronary events (ACE) was compared between the two groups. Then the patients were divided into three subgroups (S1:LDL-C ≥ 1.8 mmol/L; S2:1.4 ≤ LDL-C < 1.8 mmol/L; S3:LDL-C < 1.4 mmol/L). The correlation between Lp(a) elevations and cardiovascular risk in different subgroups was analysed by Cox proportional hazards models. RESULTS: The incidence of MACE and ACE in the high-Lp(a) group was significantly higher than those in the low-Lp(a) group (P < 0.05). Lp(a) elevations had independent prognostic value from the statistical point of view (MACE: HR = 1.63, 95%CI = 1.12-2.38, P = 0.012; ACE: HR = 1.70, 95%CI = 1.03-2.81, P = 0.037). Subgroup analysis showed that Lp(a) elevations increased cardiovascular risk when LDL-C ≥ 1.4 mmol/L. However, this correlation no longer existed when LDL-C levels were very low (< 1.4 mmol/L) (MACE: HR = 0.49, 95%CI = 0.17-1.42, P = 0.186; ACE: HR = 0.68, 95%CI = 0.18-2.61, P = 0.570). CONCLUSIONS: Lp(a) elevations are associated with recurrent cardiovascular events when LDL-C levels are high, but this association may change when LDL-C levels are extremely low. CAD patients with combination of LDL-C ≥ 1.4 mmol/L and Lp(a) elevations shall be considered as high-risk groups and require further medication for the reduction of their LDL-C levels.

Effect of an increase in Lp(a) following statin therapy on cardiovascular prognosis in secondary prevention population of coronary artery disease.

BACKGROUND: Lipoprotein (a) [Lp(a)] is an independent risk factor for coronary artery disease (CAD). Recent studies have indicated that statins tend to increase Lp(a) levels by 10-20%. However, the association of statin-mediated increases in Lp(a) levels with CAD has not been determined.  METHODS: This study included 488 patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). Lp(a) levels were measured at baseline and 1 month after statin therapy. The study endpoints were major adverse cardiovascular events (MACE). Hazard ratios for the MACE were adjusted for potential confounder using Cox regression. RESULTS: After statin therapy, the mean level of Lp(a) increased by 19.3% from baseline. Lp(a) levels increased in 307 patients (62.9%) with a median elevation of 4.1 mg/dL. Patients with an increase in Lp(a) were at higher risk for MACE than those without an increase in Lp(a) (p = 0.044). Subgroup analyses revealed that a mild-to-moderate increase in Lp(a) was not associated with MACE, whereas there was a strong correlation between the highest quartile increase in Lp(a) (≥ 10.1 mg/dL) and MACE (HR = 2.29, 95%CI = 1.36-3.84, p = 0.002). This correlation was independent of baseline Lp(a) levels but not independent of on-statin Lp(a) levels. CONCLUSIONS: Severe increases in Lp(a) following statin therapy raise the risk of MACE, but a mild-to-moderate increase in Lp(a) may not affect the cardiovascular prognosis of CAD patients. Even if the baseline Lp(a) levels are low, it is necessary to continue testing for Lp(a) concentration at least once after statin.

[Sirt3 gene knockout protects mice from Alzheimer's disease through activating autophagy].

OBJECTIVE: To investigate the protective effect of Sirt3 gene knockout on Alzheimer's disease (AD) in mice. METHODS: The animal model of AD was established by intraperitoneal injection of D-galactose and brain-localized injection of amyloid ß-protein (Aß)1-40 in wild type C57BL/6 mice and Sirt3 gene knockout mice. Morris water maze, Y maze and tail suspension test were used to assess the cognitive function and anxiety-like behaviors in mice. Aß deposition in the hippocampus was detected by immunofluorescent staining. Western blotting analysis was conducted to detect the expression of related proteins in the brain. Mouse cortical primary neurons were cultured and AD cell model was established. MTT assay was used to detect cell viability after modeling. RESULTS: Behavioral results showed that cognitive deficits were found in wide type mice after induction of AD as its prolonged escape latency (P<0.05) and decreased crossing number of platform and target zone duration (all P<0.05); while the knockout of Sirt3 alleviated cognitive deficit induced by AD (all P<0.05). Aß immunofluorescence staining showed that the deposition of Aß in the hippocampal region and expression of cleaved caspase 3 in the brain in Sirt3 knockout mice was reduced compared with that of wild type mice (all P<0.05). The expression of LC3-Ⅱ and P62 increased after AD was induced in wild type mice, while the autophagy in Sirt3 knockout mice was activated as the increase expression of LC3-Ⅱ and decrease expression of P62 (all P<0.05). In the AD cell model, the results of MTT assay were consistent with the animal experiments, and the protective effect of Sirt3 knockdown was eliminated after the treatment of the autophagy inhibitor chloroquine (all P<0.05). CONCLUSIONS: The knockdown of Sirt3 shows a protective effect on AD induced by D-galactose and Aß1-40 in mice, which may be related to its function of activating autophagy.

Impact of epicardial adipose tissue volume on hemodynamically significant coronary artery disease in Chinese patients with known or suspected coronary artery disease.

Background: Epicardial adipose tissue (EAT) is directly related to coronary artery disease (CAD), but little is known about its role in hemodynamically significant CAD. Therefore, our goal is to explore the impact of EAT volume on hemodynamically significant CAD. Methods: Patients who underwent coronary computed tomography angiography (CCTA) and received coronary angiography within 30 days were retrospectively included. Measurements of EAT volume and coronary artery calcium score (CACs) were performed on a semi-automatic software based on CCTA images, while quantitative flow ratio (QFR) was automatically calculated by the AngioPlus system according to coronary angiographic images. Results: This study included 277 patients, 112 of whom had hemodynamically significant CAD and showed higher EAT volume. In multivariate analysis, EAT volume was independently and positively correlated with hemodynamically significant CAD [per standard deviation (SD) cm3; odds ratio (OR), 2.78; 95% confidence interval (CI), 1.86-4.15; P < 0.001], but negatively associated with QFRmin (per SD cm3; ß coefficient, -0.068; 95% CI, -0.109 to -0.027; P = 0.001) after adjustment for traditional risk factors and CACs. Receiver operating characteristics curve analysis demonstrated a significant improvement in predictive value for hemodynamically significant CAD with the addition of EAT volume to obstructive CAD alone (area under the curve, 0.950 vs. 0.891; P < 0.001). Conclusion: In this study, we found that EAT volume correlated substantially and positively with the existence and severity of hemodynamically significant CAD in Chinese patients with known or suspected CAD, which was independent of traditional risk factors and CACs. In combination with obstructive CAD, EAT volume significantly improved diagnostic performance for hemodynamically significant CAD, suggesting that EAT could be a reliable noninvasive indicator of hemodynamically significant CAD.

Impact of plaque characteristics on percutaneous coronary intervention-related microvascular dysfunction: insights from angiographic microvascular resistance and intravascular ultrasound.

Background: The correlation between percutaneous coronary intervention (PCI)-related microvascular dysfunction (MVD) and plaque characteristics remains unclear. To investigate this correlation and its prognosis, we assessed changes in MVD by angiographic microvascular resistance (AMR) and intracoronary ultrasound scans after PCI. Methods: We conducted a retrospective study that enrolled 250 patients with coronary artery disease between July 2016 and December 2018. We collected demographic characteristics, laboratory tests, coronary angiography (CAG) and intracoronary ultrasound findings. We calculated quantitative flow ratio (QFR) and AMR by CAG. The endpoint was vessel-oriented composite outcomes (VOCOs). Results: After 47 exclusions, we divided 203 cases into a deteriorated group (n=139) and an improved group (n=64) based on AMR change after PCI. Compared with the improved group, the deteriorated group had smaller lumen area [3.03 (interquartile range, 2.20-3.91) vs. 3.55 mm2 (interquartile range, 2.45-4.57), P=0.033], higher plaque burden [78.92% (interquartile range, 73.95-82.61%) vs. 71.93% (interquartile range, 62.70-77.51%), P<0.001], and higher proportion of lipidic components (13.86%±4.67% vs. 11.78%±4.41%, P=0.024). Of 186 patients who completed 4.81±1.55 years follow-up, 56 developed VOCOs. Receiver-operating characteristic (ROC) curve analysis showed post-PCI AMR and VOCOs correlation (area under the curve: 0.729, P<0.001). Multivariate regression analysis showed post-PCI AMR >285 mmHg·s/m correlated with adverse outcome (hazard ratio =4.350; 95% confidence interval: 1.95-9.703; P<0.001). Conclusions: Intravascular ultrasound (IVUS) imaging and AMR revealed an association of post-PCI MVD with a smaller lumen area, more severe plaque burden, and a higher percentage of lipidic components. Post-PCI MVD was an independent risk factor for poor prognosis.