Endothelial microRNAs in INOCA patients with diabetes mellitus.

Ischemia with non-obstructive coronary artery (INOCA) is a common cause of hospital admissions, leading to negative outcomes and reduced quality of life. Central to its pathophysiology is endothelial dysfunction, which contributes to myocardial ischemia despite the absence of significant coronary artery blockage. Addressing endothelial dysfunction is essential in managing INOCA to alleviate symptoms and prevent cardiovascular events. Recent studies have identified diabetes mellitus (DM) as a significant factor exacerbating INOCA complications by promoting endothelial impairment and coronary microvascular dysfunction. MicroRNAs (miRNAs) have emerged as potential biomarkers and therapeutic targets in various biological processes, including endothelial dysfunction and cardiovascular diseases. However, research on miRNA biomarkers in INOCA patients is sparse. In this study, we examined a panel of circulating miRNAs involved in the regulation of endothelial function in INOCA patients with and without DM. We analyzed miRNA expression using RT-qPCR in a cohort of consecutive INOCA patients undergoing percutaneous coronary intervention. We detected a significant dysregulation of miR-363-5p and miR-92a-3p in INOCA patients with DM compared to those without DM, indicating their role as biomarkers for predicting and monitoring endothelial dysfunction in INOCA patients with DM.

Myocardial mass affects diagnostic performance of non-hyperemic pressure-derived indexes in the assessment of coronary stenosis.

Background Several non-hyperemic pressure-derived Indexes (NHPI) have been introduced for the assessment of coronary stenosis, showing a good correlation with fractional flow reserve (FFR). Notably, either the assessment of NHPI during adenosine administration (NHPIADO) or the Hybrid Approach (NHPIHA), combining NHPI with FFR, have been showed to increase the accuracy of such indexes. It remains unclear whether diagnostic performance might be affected by the extent of the subtended myocardial mass. METHODS: We enrolled consecutive patients with an intermediate coronary stenosis assessed with NHPI and FFR. NHPI were also measured during adenosine (ADO) administration (NHPIADO). The amount of jeopardized myocardium was assessed using the Duke Jeopardy Score (DJS). With FFR as reference, we assessed the accuracy of NHPI, NHPIADO and NHPIHA according to the extent of the subtended myocardium. RESULTS: One-hundred-seventy stenoses from 151 patients were grouped according to the DJS as follows: A) Small Extent (SE, n = 82); B) Moderate Extent (ME, n = 53); C) Large Extent (LE, n = 35). As compared with FFR, NHPI showed a significantly different accuracy, as assessed by the Youden's index, according to the extent of the jeopardized myocardium (SE: 0.39 ± 0.05, ME: 0.68 ± 0.06, LE: 0.28 ± 0.06, p < 0.001). Conversely, both the NHPIADO (SE: 0.76 ± 0.02, ME: 0.88 ± 0.02, LE: 0.82 ± 0.02, p = 0.72) and NHPIHA (SE: 0.82 ± 0.07, ME: 0.84 ± 0.02, LE: 0.88 ± 0.02, p = 0.70) allowed for a better diagnostic accuracy regardless of the amount of myocardium subtended. CONCLUSIONS: Diagnostic performance of NHPI might be affected by the extent of myocardial territory subtended by the coronary stenosis. A hybrid approach might be useful to overcome this limitation.

Global cognitive function correlates with P-wave dispersion in frail hypertensive older adults.

P-Wave Dispersion (PWD) is an ECG parameter defined as the difference between the longest and the shortest P-Wave duration. PWD has been associated with hypertension, a leading cause of age-related cognitive decline. Moreover, hypertension is associated with vascular dementia and Alzheimer's Disease. Based on these considerations, we evaluated PWD and global cognitive function in frail hypertensive older adults with a previous diagnosis of cognitive decline. We evaluated consecutive frail hypertensive patients ≥65-year-old with a Mini-Mental State Examination (MMSE) score <26. Patients with evidence of secondary hypertension, history of stroke, myocardial infarction, or therapy with beta-blockers or acetylcholinesterase inhibitors were excluded. Beta-blocker therapy causes a significant decrease in PWD; patients treated with acetylcholinesterase inhibitors were not included to avoid confounding effects on cognitive function. By examining 180 patients, we found that PWD significantly correlated with MMSE score. Strikingly, these effects were confirmed in a linear multivariate analysis with a regression model. To our knowledge, this is the first study showing that PWD correlates with global cognitive function in frail hypertensive older adults.

ADDED Index or Percentage Diameter of Residual Coronary Stenosis to Risk-Stratify Patients Presenting With STEMI.

BACKGROUND: We compared the prognostic value of the ADDED Index with visually estimated diameter (DS) of residual coronary stenosis (RS) in STEMI patients after successful PCI of the culprit lesion. Even though associated with a positive outcome, the functional assessment of non-culprit stenosis remains largely underused, especially in STEMI patients. The Angiography-DeriveD hEmoDynamic index (ADDED index) showed high accuracy to predict FFR and it might be used to better guide the diagnostic and therapeutic work-up of such patients. METHODS: We retrospectively included 596 patients grouped on the basis of either the ADDED Index (ADDED Negative (<2.23, n = 153) vs ADDED Positive (≥2.23, n = 129)) or the DS of the RS (RS Negative (<50%, n = 177) vs RS Positive (≥50%, n = 105)). Patients without any RS served as control (n = 314). Primary endpoints were: 1) major adverse cardiac events (MACE), composite of all-cause death, myocardial infarction (MI), clinically driven revascularizations (CDR); 2) non-culprit vessel oriented clinical events (VOCE), composite of all-cause death, non-culprit vessel related MI and CDR. RESULTS: At 24 months the rate of both MACE and VOCE was significantly higher in both the ADDED Positive and RS Positive groups. However, differently from patients in whom complete revascularization was deferred on the basis of the angiography (RS Negative), no additional risk was found for patients in the ADDED Negative group. CONCLUSIONS: In STEMI patients with MVD deferring treatment of RS on the basis of the ADDED index, rather than the visually estimated DS, is associated with a favorable clinical outcome.

Different age-independent effects of nutraceutical combinations on endothelium-mediated coronary flow reserve.

BACKGROUND: Some components of Nutraceuticals (NUT) such as red yeast rice and Morus alba have demonstrated positive effects on the endothelial function in hypercholesterolemic subjects. Our aim was to compare the effects of two different NUT combinations on cold pressure test (CPT) derived coronary flow reserve (CFR) assessed by transthoracic echo-Doppler. RESULTS: In a randomized, single-blind study, 28 consecutive patients with a variety of cardiovascular risk factors received NUT A (LopiGLIK®: berberine, red yeast rice powder, and leaf extract of Morus alba) or B (Armolipid Plus®: policosanol, red yeast rice, berberine, astaxantine, folic acidandcoenzyme Q10). An echo-Doppler exam with evaluation of CFR was performed at baseline, 2 h (acute test) and 30 days after daily NUT assumption. Blood sampling for metabolic profile and platelet aggregometry was performed at baseline and after 30 days of daily NUT assumption. CFR was not significantly modified at the acute test. After 30 days, CFR improved with NUT A (p < 0.0001), because of the increase of hyperemic flow velocity (p = 0.007), but not with NUT B. CFR was comparable between the two groups at baseline but became significantly higher after 30 days in NUT A (p < 0.02), with a higher CFR percent variation versus baseline (p = 0.008). Total cholesterol and LDL-cholesterol were reduced with both NUT A (p < 0.001 and p < 0.002, respectively) and B (both p < 0.02), whereas platelet aggregation did not significantly change. In the pooled group of patients, after adjusting for age and percent changes of systolic blood pressure, heart rate, LDL-cholesterol and glycemia, NUT A - but not NUT B - was independently associated with CFR changes (ß = 0.599, p = 0.003). CONCLUSIONS: LopiGLIK® improved endothelial-derived CFR, independently of the beneficial effects exerted on the lipid profile. These findings can have clinical reflections on the prevention of age-related inflammatory diseases including coronary artery disease. TRIAL REGISTRATION: (NUTRENDO)″(ClinicalTrials.gov, NCT02969070).