Lipoprotein associated- phospholipase A2 in STEMI vs. NSTE-ACS patients: a marker of cardiovascular atherosclerotic risk rather than thrombosis.

The precise role of Lipoprotein associated phospholipase A2 (Lp-PlA2) in the pathogenesis of acute coronary syndromes (ACS) and in the prediction of future cardiovascular events is still debated. So far, few data exist on the variations of Lp-PlA2 activity in ACS and especially in NSTE-ACS vs. STEMI patients, where thrombotic and atherosclerotic mechanisms could play a differential role. The aim of the present study was, then, to compare Lp-PlA2 activity according to the type of ACS presentation. METHODS: A consecutive cohort of patients undergoing coronary angiography for acute coronary syndrome (ACS) were included and divided according to presentation for non ST-segment elevation-ACS or ST-segment elevation Myocardial Infarction (STEMI). Lp-PLA2 activity was assessed in blood samples drawn at admission using the Diazyme Lp-PlA2 Activity Assay. RESULTS: We included in our study 117 patients, of whom 31 (26.5%) presented with STEMI. STEMI patients were significantly younger (p = 0.05), displayed a lower rate of hypertension (p = 0.002), previous MI (p = 0.001) and PCI (p = 0.01) and used less frequently statins (p = 0.01) and clopidogrel (p = 0.02). White blood cells and admission glycemia were increased in STEMI (p = 0.001, respectively). The prevalence and severity of CAD was not different according to ACS types, but for a higher prevalence of thrombus (p < 0.001) and lower TIMI flow (p = 0.002) in STEMI. The levels of Lp-PlA2 were significantly lower in STEMI as compared to NSTE-ACS patients, (132 ± 41.1 vs. 154.6 ± 40.9 nmol/min/mL, p = 0.01). In fact, the rate of patients with Lp-PlA2 above the median (148 nmol/min/mL) was significantly lower in STEMI patients as compared to NSTE-ACS (32.3% vs. 57%, p = 0.02, adjusted OR[95% CI] = 0.20[0.06-0.68], p = 0.010). Moreover, a direct linear relationship was observed between Lp-PlA2 and LDL-C (r = 0.47, p < 0.001), but not with inflammatory biomarkers. CONCLUSION: The present study shows that among ACS patients, the levels of Lp-PlA2 are inversely associated with STEMI presentation and thrombotic coronary occlusion, being instead increased in NSTE-ACS patients, therefore potentially representing a marker of more aggressive chronic cardiovascular disease with an increased risk of recurrent cardiovascular events.

Association of lower vitamin D levels with inflammation and leucocytes parameters in patients with and without diabetes mellitus undergoing coronary angiography.

BACKGROUND: Diabetes mellitus has been associated with a chronic low-grade inflammation and a higher risk of cardiovascular and infectious disease, that could be prevented by the effects of vitamin D. We aimed at evaluating the impact of vitamin D levels on the biomarkers of acute-phase response, inflammation and glucose metabolism in a large cohort of diabetic patients with cardiovascular disease. MATERIALS AND METHODS: Consecutive patients undergoing coronary angiography were included. Diabetes mellitus was defined as previous diagnosis, specific treatment administration (oral drug or insulin), fasting glycaemia >6.99 mmol/L or HbA1c >48 mmol/L. Glucose parameters, white blood cells, Neutrophil-to-Lymphocyte Ratio (NLR), Monocyte-to-Lymphocyte Ratio (MLR), C-reactive protein (CRP) and vitamin D were measured at admission. Vitamin D levels were measured by chemiluminescence immunoassay kit LIAISON® Vitamin D assay (Diasorin Inc). RESULTS: We included 1472 diabetic patients and 2499 non-diabetic patients that were divided according to vitamin D tertiles. Among diabetic patients, lower levels of vitamin D were associated with female gender (P = .02), obesity (P = .004), active smoking and acute presentation (P < .001) and with a more atherogenic metabolic profile. The levels of white blood cells, leucocytes subfamilies, and inflammatory parameters significantly correlated with vitamin D levels in both patients with and without diabetes (diabetic: P = .012 for WBC, P = .004 for NLR and P < .001 for MLR and C-reactive protein, non-diabetic: P < .001 for WBC; NLR, MLR and C-reactive protein, respectively). Among diabetic patients, results were confirmed at multivariate analysis with no significant interaction according to glycaemic control. CONCLUSION: The present study demonstrates that, among patients with cardiovascular disease, vitamin D deficiency is associated with metabolic dysregulation and with an elevation of cellular and humoural inflammatory parameters, especially among diabetics, although not being dependent from glycaemic control.

Low hemoglobin predicts high-platelet reactivity and major cardiovascular ischemic events at long-term follow-up among ACS patients receiving dual antiplatelet therapy with ticagrelor.

BACKGROUND: Reduced levels of hemoglobin (Hb) represent an established marker of impaired outcomes and increased cardiovascular risk in patients with coronary artery disease, challenging the management of dual antiplatelet therapy (DAPT). However, while anemia has emerged as an independent predictor of suboptimal platelet inhibition in patients receiving clopidogrel, no study has so far evaluated the impact of Hb levels on high-on treatment platelet reactivity (HRPR) with ticagrelor and their prognostic consequences, that were the aim of the present study. METHODS: Patients on DAPT with ASA + Ticagrelor (90 mg/twice a day) after percutaneous coronary revascularization for ACS were scheduled for platelet function assessment 30-90 days post-discharge. Aggregation tests were performed by multiple electrode aggregometry. Suboptimal platelet inhibition (HRPR-high residual platelet reactivity was defined if above the lower limit of normality (417 AU*min). The primary study endpoint was defined as the occurrence of major cardiovascular events (a composite of cardiovascular death, recurrent acute coronary syndrome [MI], target vessel revascularization) at longest available follow-up. RESULTS: We included 397 patients that were divided according to tertiles values of Hb (< 12.7, 12-7-14.09, ≥14.1 g/dl). Patients with lower Hb were older and displayed a more severe cardiovascular risk profile. Mean levels of platelet reactivity were enhanced in patients with lower Hb after stimulation with TRAP peptide (TRAP test, p = .03) and ADP (p = .02). Elevated platelet reactivity (HRPR) on Ticagrelor was more frequent among patients with reduced Hb (16.4% vs. 12% vs. 5.4%, p = .005, adjusted OR [95%CI] = 1.71[0.996;3.01], p = .056). At a mean follow-up of 820.9 ± 553.4 days, 21.4% of the patients experienced the primary composite endpoint, with a higher rate of events in patients with lower Hb (27.6% vs. 22.6% vs. 13.5%, p = .006, adjusted HR [95%CI] = 1.51[1.12; 2.03], p = .006), mainly driven by a higher rate of recurrent ACS. After correction for baseline differences lower Hb tertiles but not HRPR emerged as independent predictor of MACE (adjusted HR [95%CI] = 0.98[0.50; 1.92], p = .95). CONCLUSIONS: In the present study, we demonstrated that among patients on DAPT with ASA and ticagrelor after PCI for ACS, lower Hb levels are independently associated with a higher rate of HRPR and an increased rate of major ischemic events, and especially for recurrent ACS, although with no impact on survival. Neutral prognostic effect of HRPR was observed across Hb tertiles.

Impact of renin angiotensin system inhibitors on homocysteine levels and platelets reactivity in patients on dual antiplatelet therapy.

BACKGROUND AND AIMS: Dual antiplatelet therapy (DAPT) and Renin-angiotensin system inhibitors (RASi) represent the cornerstone in the treatment of patients undergoing percutaneous coronary interventions (PCI), mainly after an acute ischemic event. However, high-on treatment residual platelet reactivity (HRPR), is not infrequent despite optimal medical treatment. Homocysteine (Hcy) is a metabolite of methionine catabolism linked to atherothrombosis. Recently, a potential crosstalk between RAS and Hcy has been suggested, potentially favouring platelet aggregation and cardiovascular disease.Therefore, we aimed to investigate the impact of RASi on Hcy levels and platelet aggregation in patients on DAPT after PCI. METHODS AND RESULTS: Patients undergoing PCI on DAPT with ASA plus an ADP-antagonist (clopidogrel, ticagrelor or prasugrel), were included. RASi comprised angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB). Aggregation tests were performed by Multiple Electrode Aggregometry. We included 1210 patients, of whom 862 (71.2%) were on treatment with RASi. Overall, DAPT composition was ASA+clopidogrel in 566 (46.8%) patients, ASA+ticagrelor in 428 (35.4%) and ASA+prasugrel in 216 (17.9%). Median values of Hcy were higher in RASi patients (p = 0.006), who displayed a higher percentage of Hcy above the median value (52.4% vs. 44.8%, p = 0.019, adjustedOR [95%CI] = 1.40 [1.04-1.88], p = 0.027). No differences in HRPR rate were found according to RASi use for ASPI test (3.6% vs. 3.3%, p = 0.88) and ADP test (25.6% vs. 24.3%,p = 0.62; adjustedOR [95%CI] = 1.23 [0.89-1.70], p = 0.220) and according to ADP-antagonist type. A direct linear relationship was observed between platelet reactivity and Hcy in both patients receiving RASi and untreated ones, with higher values of platelet aggregation being observed in patients with Hcy above the median, independently from RASi administration and DAPT strategy. CONCLUSION: In patients on DAPT after PCI, RASi treatment did not emerge as an independent predictor of HRPR. However, the levels of Hcy were significantly elevated in patients on RASi and related to higher values of platelet reactivity, independently from the DAPT strategy.

Association between vitamin D deficiency and serum Homocysteine levels and its relationship with coronary artery disease.

Homocysteine (Hcy) elevation and vitamin D deficiency have emerged as potential markers of coronary artery disease (CAD). However, even tough hypovitaminosis D has been suggested to interfere with Hcy catabolism, no study has so far addressed the interaction of vitamin D and Hcy and their impact on CAD, that was the aim of present study. A cohort of consecutive patients undergoing coronary angiography in a single center were included and analyzed within the year 2019. Significant CAD was defined as at least 1 vessel stenosis > 50%, while severe CAD as left main and/or three-vessel disease. Hcy and vitamin D levels were assesssed at admission. We included 3150 patients undergoing coronary angiography at our centre, who were divided according to the quartiles values of vitamin D. Patients with lower levels of Vitamin D displayed a higher cardiovascular risk profile and a higher prevalence of CAD. We observed an inverse linear relationship between lower levels of vitamin D and higher Hcy (r = - 0.092, p < 0.001) and a higher prevalence of hyperhomocysteinemia in patients with lower quartiles values of vitamin D (p < 0.001). By forward conditional regression model, low vitamin D appeared as independent predictors of Homocysteine levels above the median (OR[95%CI] = 1.79[1.37-2.33], p < 0.001). In addition, patients with low vitamin D (below the median) and increased Hcy displayed a non-significantly higher rate of CAD (81% vs 77.7%, p = 0.13, adjusted OR[95%CI] = 1.16[0.88-1.54], p = 0.29) but a significant increase in the rate of severe left main/3-vessel CAD (37.4% vs 30.5%, p = 0.005, adjusted OR[95%CI] = 1.29[1.02-1.67], p = 0.04). Among patients with vitamin D levels above the median, Hcy levels did not impact on the prevalence and extent of CAD (77.7 vs 77.2%, p = 0.81, adjusted OR[95%CI] = 0.94[0.73-1.20], p = 0.60 for CAD and 31.8% vs 27.7%, p = 0.08, adjusted OR[95%CI] = 0.97[0.75-1.25], p = 0.81 for severe left main/3-vessel CAD). No significant interaction between Hcy and vitamin D with CAD or severe CAD was observed. The present study shows an independent inverse linear relationship between vitamin D and Hcy values. Moreover, the association of Hcy with the extent of CAD was significant only among patients with hypovitaminosis D, and not in the cohort of subjects with vitamin D levels above the median, suggesting that a normal vitamin D status can prevent the deleterious effects of hyperhomocysteinemia on coronary atherosclerosis, a hypothesis that certainly needs further confirmation in larger randomized trials.

Vitamin D levels condition the outcome benefits of renin-angiotensin system inhibitors (RASI) among patients undergoing percutaneous coronary intervention.

BACKGROUND: Vitamin D deficiency is estimated as the most common medical condition worldwide, with severe implications on survival and on several inflammatory, immune-mediated and thrombotic disorders, and especially for cardiovascular disease. Recent studies have suggested that vitamin D could directly regulate the Renin-Angiotensin System (RAS) activity, therefore potentially interfering with the pharmacological effects of RAS Inhibitors (RASI), an issue that has seldom been explored. Therefore, the aim of the present study was to evaluate the prognostic impact of the use of RASI according to vitamin D levels among patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). METHODS: Consecutive patients undergoing PCI were included. Main clinical features and chemistry parameters were assessed at admission. Vitamin D levels were measured by chemiluminescence immunoassay kit LIAISON® Vitamin D assay (Diasorin Inc). Severe deficiency was defined for 25(OH)D < 10 ng/mL. The primary study endpoint was defined as the occurrence of major cardiovascular events (MACE, a composite of death, recurrent Myocardial Infarction (MI) and target vessel revascularization) at the longest available follow-up. RESULTS: We included a total of 705 patients, that were divided according to vitamin D tertiles (< 12.7 ng/mL; 12.7-21.59 ng/mL; ≥21.6 ng/mL) and use of RASI. RASI therapy was significantly associated to arterial hypertension, creatinine, lower 25(OH)D, use of statins, diuretics, ASA and ticagrelor across vitamin D tertiles. At a median follow-up of 996 [377-1552] days, MACE occurred in 174 (24.7 %) patients. Severe hypovitaminosis D was significantly associated with a higher rate of MACE (HR[95 %CI] = 0.75[0.62-0.91], p = 0.004). The use of RASI significantly lowered the rate of MACE in patients with lower vitamin D (I tertile: 41.3 % vs 25.9 %, adjusted HR[95 %CI] = 0.43[0.26-0.73], p = 0.002); whilst a non-significant effect was observed for II and III tertiles values (18.6 %vs 29.5 %, adjusted HR[95 %CI] = 1.16[0.57-2.34], p = 0.69, and 21.2 % vs 12.6 %, adjusted HR[95 %CI] = 1.1[0.46-2.62], p = 0.83) (p int = 0.04). A similar prognostic interaction for RASI and vitamin D was observed for cardiovascular mortality and MI (p int = 0.03). CONCLUSION: Among patients undergoing PCI, the use of RASI was associated with lower risk of MACE only among patients with lower levels of vitamin D. Future larger studies are certainly warranted in order to define the prognostic implications of vitamin D supplementation on the RAS system modulation, especially among patients treated with RASI.

Impact of aging on immature platelet count and its relationship with coronary artery disease.

Despite the fact that elderly patients represent a prevalent and challenging population in the current practice, few data exist on the impact of platelet parameters on cardiovascular risk in these patients. Therefore, the aim of the present study was to evaluate the impact of age on the immature platelet count (IPC) and their relationship with CAD. We included a total of 2236 consecutive patients undergoing coronary angiography in a single center. Elderly patients (age ≥ 75 years) were 756 (33.7%). IPC was measured at admission. Elderly patients were more often females (p < .001), with lower BMI and prevalence of smokers (p < .001), and a more complex cardiovascular risk profile and coronary disease (p = .02). Platelet count decreased with aging (p = .05), whereas no difference in the mean IPC was found between patients < or ≥75 years. In fact, advanced age did not emerge as an independent predictor of IPC above III tertile (≥8.6*10^6/ml), (adjusted OR[95%CI] = 0.97[0.78-1.21], p = .79). When considering elderly patients according to tertiles values of IPC (<5.1,5.1-8.59; ≥8.6*10^6/ml), we found no impact of IPC on the prevalence of CAD (81.1% vs 84.5% vs 81.5%, p = .92; adjusted OR[95%CI] = 1.08[0.67-1.72], p = .75) and its extent (37.7% vs 34.5% vs 40.2%, p = .57; adjusted OR[95%CI] = 1.22[0.85-1.73], p = .28). However, we observed a higher rate of calcified and type C lesions in elderly patients with higher IPC (p = .03 and p < .001, respectively). Therefore, advanced age is not associated with higher immature platelet count and the prevalence and severity of CAD. Moreover, IPC does not contribute to explain the higher prevalence and extent of coronary artery disease observed in elderly patients.

Antiplatelet Effect of Low-Dose Prasugrel in Elderly Patients Undergoing Percutaneous Coronary Interventions.

BACKGROUND: Low-dose prasugrel (5 mg) has been proposed for patients with Acute Coronary Syndrome (ACS) and advanced age or low body weight. However, the routine use of dose-adjusted prasugrel in this high-risk subset of patients is still debated. AIM: This study aimed to assess the prevalence and predictors of HRPR among elderly patients treated with low-dose (5 mg) prasugrel to evaluate the routine use of dose-adjusted prasugrel in this high-risk subset of patients. METHODS: We included 59 elderly patients (≥75 years) treated with Dual Antiplatelet Therapy (DAPT: acetylsalicylic acid (ASA) 100-160 mg + prasugrel 5 mg) after Percutaneous Coronary Interventions (PCI) and undergoing platelet function assessment (by whole blood impedance aggregometry) 30-90 days post-discharge. RESULTS: At a median follow-up of 43 days (interquartile range-IQR: 32-54), high-on treatment residual platelet reactivity (HRPR) occurred in 25 patients (42.4%), who displayed a greater body mass index (BMI) (p=0.02), lower levels of vitamin D (p=0.05) and were more frequently treated with nitrates (p=0.03). After multivariate analysis, BMI was the only independent predictor of prasugrel HRPR, and a BMI >26 was the best cut-off for predicting HRPR (adjusted Odds Ratio - OR=8.6, 95%CI: 2.2-33.9, p=0.002). CONCLUSION: Among elderly patients receiving DAPT after PCI, HRPR is common with low-dose prasugrel. A greater BMI, especially for values ≥26, is the only independent predictor of HRPR with prasugrel 5 mg.

ASA Allergy and Desensitization Protocols in the Management of CAD: A Review of Literature.

Acetylsalicylic acid (ASA) hypersensitivity still represents one of the major deals for patients with atherosclerotic cardiovascular disease (ASHD), especially for those requiring percutaneous coronary interventions in the absence of validated alternative options. Despite symptoms after ASA administration being reported in 6-20% of cases, true ASA allergy only represents a minority of the patients, pointing to the importance of challenge tests and potential strategies for tolerance induction. ASA desensitization protocols were proposed several decades ago, with accumulating the literature on their use in patients undergoing PCI either for chronic disease or acute coronary syndromes. Nevertheless, the promising results of the studies and meta-analyses have not been validated so far by the support of large-scale randomized trials or unique indications from guidelines. Therefore, ASA desensitization is still largely unapplied, leaving the management of ASA hypersensitivity to the individualized approach of cardiologists.

Optimization of the pharmacological therapy in patients with poly-vascular disease: A multidisciplinary approach.

The recent shift of the concept of cardiovascular disease as a chronic progressive condition, potentially involving multiple districts, has driven attention to the optimal management of patients with concomitant coronary and peripheral artery disease, representing a subset of patients with an increased risk of events and impaired survival. Recent pharmacological achievements in terms of antithrombotic therapy and lipid-lowering drugs allow multiple therapeutical combinations, thus requiring optimizing the treatment in a tailored fashion according to patients' risk profiles. Nevertheless, data dedicated to this specific subset of patients are still modest. We summarize currently available strategies and indications for the management of antithrombotic and lipid-lowering drugs in patients with the poly-vascular disease.

Impact of renal failure and high-platelet reactivity on major cardiovascular ischemic events among patients with acute coronary syndrome receiving dual antiplatelet therapy with ticagrelor.

BACKGROUND: No study has so far evaluated the impact of chronic kidney disease (CKD) on high-on treatment platelet reactivity (HRPR) with ticagrelor and their prognostic consequences, that were therefore the aim of the present study. METHODS: Patients on dual antiplatelet therapy with ASA+ticagrelor (90mg/twice a day) after percutaneous coronary revascularization for ACS were scheduled for platelet function assessment 30-90 days post-discharge. The primary study endpoint was defined as the occurrence of major cardiovascular events (a composite of cardiovascular death, recurrent acute coronary syndrome (MI), target vessel revascularization) at the longest available follow-up. RESULTS: We included 396 patients, that were divided according to CKD (eGFR

Managing Congenital Heart Defects in Elderly: The Platypnea-Orthodeoxia Syndrome in Underestimated Patent Foramen Ovale.

The platypnea-orthodeoxia syndrome (POS) is a rare and often suboptimally managed condition with a complex diagnostic workup, conversely displaying an easy treatment and a good recovery of symptoms, especially if consequent to an intracardiac shunt. However, its identification is challenging, due to the several clinical manifestations, the multiple etiologies, representing often the delayed presentation of a congenital heart disease. We present a case report and review of available literature on patients with the POS secondary to a patent foramen ovale successfully treated with its closure.

Impact of age on pre-procedural TIMI flow in STEMI patients undergoing primary percutaneous coronary intervention.

BACKGROUND: Advanced age is a major determinant of impaired prognosis among patients with ST-segment elevation myocardial infarction (STEMI). However, the mechanisms associated with suboptimal reperfusion and enhanced complications are still largely undefined. The aim of the present study was to assess the impact of age on the angiographic findings and the procedural results of primary percutaneous coronary intervention (pPCI) in patients with STEMI. METHODS: A consecutive cohort of patients admitted for STEMI treated with pPCI were included. Infarct-related artery (IRA) patency was defined for preprocedural TIMI flow 3. RESULTS: We included 520 patients, divided according to age tertiles (<61; 61-72; ≥73). Elderly patients were more often females, with hypertension, renal failure, prior myocardial infarction or PCI, with lower rates of smoking history, haemoglobin, leukocytes and cholesterol (P < 0.001), lower ejection fraction (P = 0.02), higher use of renin angiotensin system inhibitors, statins, ASA, calcium antagonists, diuretics and beta blockers. At angiography, for the IRA, percentage of thrombus (P = 0.02) and stenosis (P = 0.01), direct stenting (P = 0.02) and glycoprotein IIb-IIIa inhibitors (P = 0.04) inversely related with age, but for higher restenosis (P = 0.04). IRA patency was more common in patients aged ≥73 years (27.9% vs. 32.3% vs. 41.1%, P = 0.01). The impact of age on preprocedural TIMI flow was confirmed at multivariate analysis [adjusted odds ratio (95% confidence interval) = 0.68 (0.47-0.98), P = 0.04]. CONCLUSION: The present study shows that among STEMI patients undergoing primary PCI, more advanced age represents an independent predictor of preprocedural IRA patency. Future studies will define the implications on procedural results and long-term prognosis.

Prognostic Impact of Drug-Coated Balloons in Patients With Diabetes Mellitus: A Propensity-Matched Study.

Patients with diabetes mellitus (DM) are at higher risk of restenosis and stent thrombosis after percutaneous coronary intervention (PCI) and drug-eluting stent (DES) positioning. Whether drug-coated balloons (DCB) can offer any benefit in this subset of patients has been seldom cleared out and was the aim of the present propensity-matched cohort study, that compared the prognostic impact of DCB versus DES in patients with DM who underwent PCI. Patients with DM enrolled in the NOvara-BIella-TREnto (NOBITRE) Registry were identified and matched according to propensity score, to a control population of patients with DM treated with DES. The primary study end point was the occurrence of major adverse cardiovascular events (MACEs). A total of 150 patients were identified in the DCB group and matched with 150 DES-treated patients. Patients treated with DCB displayed more often a previous cardiovascular history and received a more complete pharmacological therapy. Target vessel diameter and the percentage of stenosis were lower in patients with DCB, whereas binary in-stent restenosis was more common (p <0.001, p = 0.003, and p <0.001, respectively). Paclitaxel-eluting balloon represented the most common strategy in the DCB group, whereas Zotarolimus-eluting stents were used in half of the DES population. At a median follow-up of 545.5 days, MACE occurred in 54 (19.4%) of patients, with no difference according to the PCI strategy (21.6% vs 17.3%, adjusted hazard ratio [95% confidence interval] 1.51 [0.46 to 4.93], p = 0.50). Major ischemic end points were slightly increased in patients treated with DCB, whereas overall death was significantly reduced (3.6% vs 10.9%; adjusted hazard ratio [95% confidence interval] 0.27 [0.08 to 0.91], p = 0.03). In conclusion, the present propensity-matched study shows that, in patients with DM who underwent PCI for in-stent restenosis or de novo lesions, the use of DCB is associated with a similar rate of MACE and a modest increase in target lesion failure, but a significantly improved survival as compared with DES.

Characteristics of patients with recurrent acute myocardial infarction after MINOCA.

BACKGROUND: Myocardial infarction (MI) with non-obstructed coronary arteries (MINOCA) is an increasingly recognized condition with challenging management. Some MINOCA patients ultimately experience recurrent acute MI (re-AMI) during follow-up; however, clinical and angiographic factors predisposing to re-AMI are still poorly defined. METHODS: In this retrospective multicenter cohort study we enrolled consecutive patients fulfilling diagnostic criteria of MINOCA according to the IV universal definition of myocardial infarction; characteristics of patients experiencing re-AMI during the follow-up were compared to a group of MINOCA patients without re-AMI. RESULTS: 54 patients (mean age 66 ± 13) experienced a subsequent re-AMI after MINOCA and follow-up was available in 44 (81%). Compared to MINOCA patients without re-AMI (n = 695), on first invasive coronary angiography (ICA) MINOCA patients with re-AMI showed less frequent angiographically normal coronaries (37 versus 53%, p = 0.032) and had a higher prevalence of atherosclerosis involving 3 vessels or left main stem (17% versus 8%, p = 0.049). Twenty-four patients (44%) with re-AMI underwent a new ICA: 25% had normal coronary arteries, 12.5% had mild luminal irregularities (<30%), 20.8% had moderate coronary atherosclerosis (30-49%), and 41.7% showed obstructive coronary atherosclerosis (≥50% stenosis). Among patients undergoing new ICA, atherosclerosis progression was observed in 11 (45.8%), 37.5% received revascularization, only 4.5% had low-density lipoprotein cholesterol (LDL_C) under 55 mg/dL and 33% experienced a new cardiovascular disease (CVD) event (death, AMI, heart failure, stroke) at subsequent follow-up. CONCLUSIONS: In the present study, only a minority of MINOCA patients with re-AMI underwent a repeated ICA, nearly one out of two showed atherosclerosis progression, often requiring revascularization. Recommended LDL-C levels were achieved only in a minority of the cases, indicating a possible underestimation of CVD risk in this population.

Low levels of vitamin D and coronary artery disease: Is it time for therapy?

The association between vitamin D and the prevalence and severity of coronary artery disease (CAD), major established cardiovascular risk factors, and acute ischemic events has been consistently demonstrated in large-scale observational studies and meta-analyses, with relevant prognostic implications. The rise in prevalence of hypovitaminosis D in recent years, reaching pandemic pro-portions, has pointed to the importance of the identification and optimization of the indications and strategies for the therapeutic use of vitamin D, with particular relevance for cardiovascular health. However, vitamin D supplementation has provided so far inconsistent results in primary prevention, with even fewer data reported in patients with established CAD. The present review aims to provide an updated overview of the available evidence and potential therapeutic applications of vitaminD in patients with CAD.

Optimal dual antiplatelet therapy strategy in elderly patients with acute coronary syndrome.

One out of three hospitalizations for acute coronary syndrome (ACS) involve nowadays elderly patients, carrying together a significant burden of comorbidities and a higher risk of complications. In particular, both ischemic and haemorrhagic risk are markedly enhanced in advanced age, and strictly interconnected, challenging the management of dual antiplatelet therapy (DAPT) in these patients. The recent development of several therapeutic options in terms of duration and combination of antiplatelet agents have offered a wider spectrum of opportunities for a more individualized approach in the management of DAPT after an ACS, although the criteria for the selection of the most appropriate strategy in each patient still lack validation. In particular, dose-adjustment, early aspirin discontinuation, laboratory-driven tailoring and shorter or extended DAPT have been addressed with promising safety and efficacy results. The present review provides an updated overview on the emerging evidencefrom randomized clinical trials and subanalyses dedicated to the management of DAPT in elderly patients presenting with ACS.

Impact of aging on the effects of intracoronary adenosine, peak hyperemia and its duration during fractional flow reserve assessment.

INTRODUCTION: Functional assessment of coronary stenoses is crucial for determining the correct therapeutic strategy. Age-related modifications in cardiovascular function could alter the functional significance of an intermediate coronary lesion. Therefore, the aim of the present study was to investigate the impact of age on fractional flow reserve (FFR) measurements in patients with intermediate coronary artery disease. METHODS: We included patients undergoing coronary angiography at our Division of Cardiology from June 2008 to February 2019 for elective indication or recent acute coronary syndrome and receiving FFR assessment for an intermediate coronary stenosis (angiographic 40-70% stenoses). FFR measurement was performed by pressure-recording guidewire (Prime Wire; Volcano Imaging System Philips Healthcare, San Diego, California, USA), after induction of hyperemia with intracoronary boluses of adenosine (from 60 to 720 µg, with dose doubling at each step). RESULTS: We included in our study 276 patients, undergoing FFR evaluation on 314 lesions, that were divided according to age (< or ≥70 years). Elderly patients displayed a higher cardiovascular risk profile and received more often specific therapy. We found significantly higher FFR values and lower Delta FFR and time to recovery in patients with age ≥70 years old even with high-dose adenosine. Elderly patients showed a trend in lower percentage of positive FFRs, especially with high-dose (P = 0.09). Overall, any FFR ≤ 0.80 was observed in 33.5% of younger patients and 21.1% of patients ≥70 years (P = 0.02). Results were confirmed after correction for baseline differences [adjusted odds ratio (95% confidence interval) = 0.60 (0.33-1.09), P = 0.08]. CONCLUSION: This is one of the first studies investigating the impact of age on the measurement of FFR with high-dose adenosine. Patients with age >70 years old with intermediate CAD are more likely to have higher FFR values and lower duration of hyperemia after adenosine boluses, as compared with younger patients.

Preprocedural ß-Blockers in the Functional Assessment of Intermediate Coronary Lesions by Instantaneous Wave-Free Ratio.

AIM: Instantaneous wave-free ratio (iFR) has emerged as the strategy of choice for the assessment of intermediate coronary lesions. The impact of preprocedural ß-blockers therapy on the iFR was the aim of this study. METHODS: We included patients undergoing functional assessment of intermediate (40%-70%) coronary lesions in 2 centers. The iFR measurement was performed by pressure-recording guidewire and calculated at the core laboratory using the manufacturers' dedicated software. Minimal luminal diameter, reference diameter, percent diameter stenosis, and length of the lesion were measured. Positive iFR was considered for values <0.90. RESULTS: We included 197 patients undergoing functional evaluation of 223 coronary lesions. Patients on ß-blockers (69%) had more frequently hypertension (P = .05); previous myocardial infarction (P = .01); therapy with clopidogrel (P = .02), statins, and aspirin; and acute coronary syndrome at presentation (P < .001, respectively). Mean iFR values were slightly higher in patients on ß-blockers (0.94 ± 0.06 vs 0.92 ± 0.06, P = .11). The rate of positive iFR was significantly lower with ß-blockers (14.9% vs 27.5%, P = .04). On multivariate analysis, ß-blockers use was a predictor of the significance of coronary stenoses (odds ratio [OR] = 0.48; 95% CI = 0.23-0.98; P = .05) together with lesion length (OR = 1.04; 95% CI = 1.01-1.07; P = .007). CONCLUSION: Among patients undergoing iFR, preprocedural ß-blockers are associated with higher absolute values and a lower rate of positive iFR.

Impact of Age on the Functional Evaluation of Intermediate Coronary Stenoses With Instantaneous Wave-Free Ratio and Fractional Flow Reserve.

The optimal strategy for assessing the ischemic significance of intermediate coronary stenoses with adenosine-induced fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) is still debated. Few studies have previously assessed the impact of age on FFR and iFR, which was the aim of our study. Patients undergoing FFR and iFR evaluation for intermediate (40%-70%) coronary lesions were included and divided according to age. Fractional flow reserve was performed by intracoronary boluses of adenosine (60-1440 µg). Instantaneous wave-free ratio was automatically calculated. Among 148 patients undergoing FFR measurement of 166 lesions, 45.3% were ≥70 years. Elderly patients had higher minimal lumen diameter (P = .03). We also observed a linear relationship between iFR and FFR independently of age. Fractional flow reserve values were higher in the elderly patients, whereas iFR was not related to age. A total of 33 lesions had a positive iFR with no difference for age (17.3% vs 22%, P = .56), while FFR <0.80 was more infrequent in the elderly patients (17.1% vs 34.8%, P = .02). In intermediate coronary stenoses, iFR and FFR correlation is unaffected by age. Fractional flow reserve is higher in the elderly patients, whereas iFR is less affected by age. Future large-scale studies are needed to define whether iFR should be the preferred choice in elderly patients.