Vitamin D and Cardiovascular Diseases: From Physiology to Pathophysiology and Outcomes.

Vitamin D is rightly recognized as an essential key factor in the regulation of calcium and phosphate homeostasis, affecting primary adequate bone mineralization. In the last decades, a more complex and wider role of vitamin D has been postulated and demonstrated. Cardiovascular diseases have been found to be strongly related to vitamin D levels, especially to its deficiency. Pre-clinical studies have suggested a direct role of vitamin D in the regulation of several pathophysiological pathways, such as endothelial dysfunction and platelet aggregation; moreover, observational data have confirmed the relationship with different conditions, including coronary artery disease, heart failure, and hypertension. Despite the significant evidence available so far, most clinical trials have failed to prove any positive impact of vitamin D supplements on cardiovascular outcomes. This discrepancy indicates the need for further information and knowledge about vitamin D metabolism and its effect on the cardiovascular system, in order to identify those patients who would benefit from vitamin D supplementation.

The impact of time since SARS-Cov-2 vaccination, age, sex and comorbidities on COVID-19 outcome in hospitalized patients with SARS-CoV-2 infection.

We evaluated the impact of COVID-19 vaccination on disease outcome in hospitalized patients with SARS-CoV-2 infection with a prospective study. 745 vaccinated and 451 unvaccinated patients consecutively admitted to a COVID-19 Hospital from 1st September 2021 to 1st September 2022 were included. Compared with unvaccinated cases, vaccinated patients were older, had more comorbidities, but had a lower risk of O2 need (odds ratio, OR, 0.46; 95 % CI 0.32-0.65) by logistic regression analysis adjusted for age, sex, comorbidity and WHO COVID-19 Clinical Progression Scale at admission. The ORs for O2 need were 0.38 (0.24-0.61), 0.50 (0.30-0.83) and 0.57 (0.34-0.96) in patients vaccinated 14-120, 121-180 and > 180 days prior to hospitalization, respectively. An anti-spike Ig titer higher than 5000 U/ml was associated with a reduced risk of O2 need (OR 0.52; 95 % CI 0.30-0.92). This study shows that COVID-19 vaccination has a significant impact on COVID-19 outcomes in hospitalized patients.

Prognostic significance of the wall to lumen ratio of retinal arterioles evaluated by adaptive optics.

OBJECTIVE: Microvascular structural alterations may be considered an important form of hypertension-mediated organ damage. An increased media-to-lumen ratio of subcutaneous small arteries evaluated with locally invasive techniques (micromyography) predicts the development of cardiovascular (CV) events. However, it is not known whether retinal arteriole structural alterations evaluated with a noninvasive approach (Adaptive Optics) may have a prognostic significance. DESIGN AND METHODS: Two-hundred and thirty-seven subjects (mean age 58.7 ± 16.1 years, age range 13-89 years; 116 males) were included in the study: 65 normotensive subjects (27.4 %) and 172 patients with essential hypertension or primary aldosteronism (72.6 %). All subjects underwent a non-invasive evaluation of retinal arteriolar wall-to-lumen ratio (WLR) by Adaptive Optics. Subjects were re-evaluated after an average follow-up time of 4.55 years in order to assess the occurrence of clinical events (non CV and/or CV death or events). RESULTS: Fifty-four events occurred in the study population:26 were cardio-cerebrovascular events (ischemic or hemorragic stroke, atrial fibrillation, heart failure, coronary artery disease, peripheral artery disease, cardiac valvular disease) while the remaining were deaths for any cause, or neoplastic diseases. Subjects with events were older and had a WLR of retinal arterioles significantly greater than those without events. The event-free survival was significantly worse in those with a baseline WLR above the median value of the population (0.28) according to Kaplan-Mayer survival curves and multivariate analysis (Cox's proportional hazard model). The evidence was confirmed after restricting the analysis to CV events. CONCLUSIONS: Structural alterations of retinal arterioles evaluated by Adaptive Optics may predict total and CV events.

Impact of Immunity on Coronary Artery Disease: An Updated Pathogenic Interplay and Potential Therapeutic Strategies.

Coronary artery disease (CAD) is the leading cause of death worldwide. It is a result of the buildup of atherosclerosis within the coronary arteries. The role of the immune system in CAD is complex and multifaceted. The immune system responds to damage or injury to the arterial walls by initiating an inflammatory response. However, this inflammatory response can become chronic and lead to plaque formation. Neutrophiles, macrophages, B lymphocytes, T lymphocytes, and NKT cells play a key role in immunity response, both with proatherogenic and antiatherogenic signaling pathways. Recent findings provide new roles and activities referring to endothelial cells and vascular smooth muscle cells, which help to clarify the intricate signaling crosstalk between the involved actors. Research is ongoing to explore immunomodulatory therapies that target the immune system to reduce inflammation and its contribution to atherosclerosis. This review aims to summarize the pathogenic interplay between immunity and CAD and the potential therapeutic strategies, and explore immunomodulatory therapies that target the immune system to reduce inflammation and its contribution to atherosclerosis.

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.

Platelets and the Atherosclerotic Process: An Overview of New Markers of Platelet Activation and Reactivity, and Their Implications in Primary and Secondary Prevention.

The key role played by platelets in the atherosclerosis physiopathology, especially in the acute setting, is ascertained: they are the main actors during thrombus formation and, thus, one of the major investigated elements related to atherothrombotic process involving coronary arteries. Platelets have been studied from different points of view, according with the technology advances and the improvement in the hemostasis knowledge achieved in the last years. Morphology and reactivity constitute the first aspects investigated related to platelets with a significant body of evidence published linking a number of their values and markers to coronary artery disease and cardiovascular events. Recently, the impact of genetics on platelet activation has been explored with promising findings as additional instrument for patient risk stratification; however, this deserves further confirmations. Moreover, the interplay between immune system and platelets has been partially elucidated in the last years, providing intriguing elements that will be basic components for future research to better understand platelet regulation and improve cardiovascular outcome of patients.

New Insights into Pathophysiology and New Risk Factors for ACS.

Cardiovascular disease still represents the main cause of mortality worldwide. Despite huge improvements, atherosclerosis persists as the principal pathological condition, both in stable and acute presentation. Specifically, acute coronary syndromes have received substantial research and clinical attention in recent years, contributing to improve overall patients' outcome. The identification of different evolution patterns of the atherosclerotic plaque and coronary artery disease has suggested the potential need of different treatment approaches, according to the mechanisms and molecular elements involved. In addition to traditional risk factors, the finer portrayal of other metabolic and lipid-related mediators has led to higher and deep knowledge of atherosclerosis, providing potential new targets for clinical management of the patients. Finally, the impressive advances in genetics and non-coding RNAs have opened a wide field of research both on pathophysiology and the therapeutic side that are extensively under investigation.

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

The mega COMBO collaboration: An individual patient data pooled analysis of patients undergoing PCI with COMBO stent.

BACKGROUND: COMBO (OrbusNeich Medical, Hong Kong) is a dual-therapy coronary stent featuring sirolimus as antiproliferative drug and an anti-CD34+ antibody coating to attract endothelial progenitor cells favoring rapid stent re-endothelization. The Mega COMBO collaboration aimed to evaluate the performance of the COMBO stent in a large contemporary cohort of patients undergoing percutaneous coronary intervention (PCI). METHODS: Patient-level data of subjects undergoing PCI with the COMBO stent from the REMEDEE-Trial, REMEDEE-OCT, HARMONEE, REDUCE, SORT OUT X, REMEDEE-Registry and MASCOT studies were pooled together. The primary endpoint was 1-year target lesion failure (TLF), a composite of cardiovascular death, target vessel myocardial infarction (TV-MI) or clinically driven target lesion revascularization (CD-TLR). Secondary outcomes were the individual components of the primary endpoint and stent thrombosis (ST). Endpoints were evaluated against performance goals based on the EAPCI (the European Association of Percutaneous Coronary Intervention) recommendations for new drug-eluting stents. RESULTS: A total of 6753 patients (mean age 63.7 ± 11.4 years, 23% women) were included. At 1-year follow-up, TLF occurred in 303 (4.6%) patients. The rates of cardiovascular death, TV-MI, and CD-TLR were 1.3%, 1.8%, and 2.5%, respectively. The rate of definite/probable ST was 0.73%, early ST (<1 month) was 0.48%, while late ST (1-12 months) was 0.26%. The performance goals were met for all of the evaluated endpoints. CONCLUSIONS: This large patient-level pooled analysis provides a comprehensive outline of the performance of the dual-therapy COMBO stent. The low rates of primary and secondary endpoints suggest that this stent technology may be a good alternative to other contemporary drug eluting coronary stent platforms.

Skin capillary alterations in patients with acute SarsCoV2 infection.

BACKGROUND: Acute SarsCov2 infection is associated with endothelial dysfunction and 'endothelitis', which might explain systemic microvascular impairment. The presence of endothelial damage may promote vasoconstriction with organ ischemia, inflammation, tissue oedema and a procoagulant state resulting in an increase in the incidence of cardiovascular and cerebrovascular events. Microvascular thrombosis has been demonstrated in postmortem autopsy of COVID-19 patients; however, few data are available about skin capillary alterations in these patients. MATERIALS AND METHODS: We evaluated skin microvascular alteration in 22 patients admitted to our hospital with SarsCov2 infection. Capillary density was evaluated by capillaroscopy in the nailfold and the dorsum of the finger in the acute phase of the disease. Capillaroscopy was repeated after 3 months (recovery phase). In addition, blood chemistry parameters and inflammatory markers were obtained during acute infection and at the recovery after 3 months. RESULTS: Patients with COVID-19 showed skin microvascular complications, such as thrombosis, microhaemorrhages and neoangiogenesis, which were not detected after 3 months from the discharge. A significant reduction of capillary density in the dorsum was observed after 3 months from the acute infection (97.2 ±â€Š5.3 vs. 75.81 ±â€Š3.9 n/mm 2P  < 0.05). A significant inverse correlation between C-reactive protein and capillary density was observed in patients with acute SarsCov2 infection ( r  = 0.44, P  < 0.05). Conversely a direct correlation between capillary density during the acute phase and lymphocyte number was detected ( r  = 0.49, P  < 0.05). CONCLUSION: This is the first in-vivo evidence of skin capillary thrombosis, microhaemorrhages and angiogenesis in patients with acute SarsCov2 infection, which disappeared after 3 months, supporting the presence of endothelial dysfunction and inflammation. Capillary alterations might reflect systemic vascular effects of viral infection.

Impact of chronic obstructive pulmonary disease on short-term outcome in patients with ST-elevation myocardial infarction during COVID-19 pandemic: insights from the international multicenter ISACS-STEMI registry.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is projected to become the third cause of mortality worldwide. COPD shares several pathophysiological mechanisms with cardiovascular disease, especially atherosclerosis. However, no definite answers are available on the prognostic role of COPD in the setting of ST elevation myocardial infarction (STEMI), especially during COVID-19 pandemic, among patients undergoing primary angioplasty, that is therefore the aim of the current study. METHODS: In the ISACS-STEMI COVID-19 registry we included retrospectively patients with STEMI treated with primary percutaneous coronary intervention (PCI) between March and June of 2019 and 2020 from 109 high-volume primary PCI centers in 4 continents. RESULTS: A total of 15,686 patients were included in this analysis. Of them, 810 (5.2%) subjects had a COPD diagnosis. They were more often elderly and with a more pronounced cardiovascular risk profile. No preminent procedural dissimilarities were noticed except for a lower proportion of dual antiplatelet therapy at discharge among COPD patients (98.9% vs. 98.1%, P = 0.038). With regards to short-term fatal outcomes, both in-hospital and 30-days mortality occurred more frequently among COPD patients, similarly in pre-COVID-19 and COVID-19 era. However, after adjustment for main baseline differences, COPD did not result as independent predictor for in-hospital death (adjusted OR [95% CI] = 0.913[0.658-1.266], P = 0.585) nor for 30-days mortality (adjusted OR [95% CI] = 0.850 [0.620-1.164], P = 0.310). No significant differences were detected in terms of SARS-CoV-2 positivity between the two groups. CONCLUSION: This is one of the largest studies investigating characteristics and outcome of COPD patients with STEMI undergoing primary angioplasty, especially during COVID pandemic. COPD was associated with significantly higher rates of in-hospital and 30-days mortality. However, this association disappeared after adjustment for baseline characteristics. Furthermore, COPD did not significantly affect SARS-CoV-2 positivity. TRIAL REGISTRATION NUMBER: NCT04412655 (2nd June 2020).

Angiographic and clinical outcome of SARS-CoV-2 positive patients with ST-segment elevation myocardial infarction undergoing primary angioplasty: A collaborative, individual patient data meta-analysis of six registry-based studies.

BACKGROUND: The characteristics and outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients with ST-Elevation Myocardial Infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) are still poorly known. METHODS: The PANDEMIC study was an investigator-initiated, collaborative, individual patient data (IPD) meta-analysis of registry-based studies. MEDLINE, ScienceDirect, Web of Sciences, and SCOPUS were searched to identify all registry-based studies describing the characteristics and outcome of SARS-CoV-2-positive STEMI patients undergoing PPCI. The control group consisted of SARS-CoV-2-negative STEMI patients undergoing PPCI in the same time period from the ISACS-STEMI COVID 19 registry. The primary outcome was in-hospital mortality; the secondary outcome was postprocedural reperfusion assessed by TIMI flow. RESULTS: Of 8 registry-based studies identified, IPD were obtained from 6 studies including 941 SARS-CoV-2-positive patients; the control group included 2005 SARS-CoV-2-negative patients. SARS-CoV-2-positive patients showed a significantly higher in-hospital mortality (p < 0.001) and worse postprocedural TIMI flow (<3, p < 0.001) compared with SARS-CoV-2-negative subjects. The increased risk for SARS-CoV-2-positive patients was significantly higher in males compared to females for both the primary (pinteraction = 0.001) and secondary outcome (pinteraction = 0.023). In SARS-CoV-2-positive patients, age ≥ 75 years (OR = 5.72; 95%CI: 1.77-18.5), impaired postprocedural TIMI flow (OR = 11.72; 95%CI: 2.64-52.10), and cardiogenic shock at presentation (OR = 11.02; 95%CI: 2.84-42.80) were independent predictors of mortality. CONCLUSIONS: In STEMI patients undergoing PPCI, SARS-CoV-2 positivity is independently associated with impaired reperfusion and with a higher risk of in-hospital mortality, especially among male patients. Age ≥ 75 years, cardiogenic shock, and impaired postprocedural TIMI flow independently predict mortality in this high-risk 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.

Impact of Small Valve Size on 1-Year Outcomes After Transcatheter Aortic Valve Implantation in Women (from the WIN-TAVI Registry).

Although most patients with small aortic annulus are women, there is paucity of data on the prognostic impact of small aortic prosthesis in women who underwent transcatheter aortic valve implantation (TAVI). Therefore, we aimed to evaluate the impact of small valve size on 1-year clinical outcomes after TAVI in women. The Women's INternational Transcatheter Aortic Valve Implantation is an all-women registry evaluating patients with severe aortic stenosis who underwent TAVI. Based on the size of the aortic bioprosthesis implanted, women were stratified into small (≤23 mm) and nonsmall (>23 mm) valve. The primary efficacy endpoint was the Valve Academic Research Consortium-2 composite of all-cause death, stroke, myocardial infarction, hospitalization for valve-related symptoms or heart failure or valve-related dysfunction at 1-year follow-up. Of 934 women who underwent TAVI, 388 (41.5%) received a small valve. Women with a small valve size had a lower body mass index, lower surgical risk scores, were less likely to suffer from atrial fibrillation, less often required postdilation and had a lower rate of residual aortic regurgitation grade ≥2. The occurrence of the Valve Academic Research Consortium-2 efficacy endpoint was similar between women treated with small and nonsmall valve (16.0% vs 16.3%, p = 0.881; adjusted hazard ratio 1.34, 95% confidence interval 0.90 to 2.00). Likewise, there were no significant differences in the occurrence of other secondary endpoints after multivariable adjustment. In conclusion, women with severe aortic stenosis who underwent TAVI with the implantation of a small valve bioprosthesis had similar 1-year outcomes as those receiving a nonsmall bioprosthesis.

Perioperative management of P2Y12 inhibitors in patients undergoing cardiac surgery within 1 year of PCI.

AIMS: To evaluate the impact of perioperative P2Y12 receptor inhibitor therapy among patients undergoing cardiac surgery within 1 year of percutaneous coronary intervention (PCI). METHODS AND RESULTS: Patients undergoing cardiac surgery in the year post-PCI at three tertiary care centres between 2011 and 2018 were stratified into those who had received at least one dose of P2Y12 inhibitor prior to surgery (within 5 days for clopidogrel or prasugrel, or within 3 days for ticagrelor) and those who had not. The outcomes of interest were major adverse cardiac and cerebrovascular events (MACCEs) and bleeding. Among 20 279 PCI patients, 359 (1.8%) underwent cardiac surgery in the ensuing year, 76.3% of whom received coronary artery bypass grafts. Overall, 33 (9.2%) MACCEs and 85 (23.7%) bleeding events occurred within 30 days post-cardiac surgery. Perioperative P2Y12 inhibition (N = 133, 37%) was not associated with the risk of MACCEs or bleeding, despite numerically lower rates of myocardial infarction or stent thrombosis (0.0% vs. 2.6%; P = 0.089). Patients who continued the P2Y12 inhibitor until the day of surgery (N = 60, 17%) had significantly higher bleeding risk [adjusted odds ratio 2.93, 95% confidence interval 1.53-5.59)]. Predictors of MACCEs included a time interval from PCI to cardiac surgery of ≤30 days and reduced ejection fraction, whereas urgent/emergent surgery predicted bleeding. Chronic kidney disease and myocardial infarction as indication for PCI predicted both MACCEs and bleeding. CONCLUSION: Among patients undergoing cardiac surgery in the year after PCI, the perioperative risk of ischaemic and bleeding events might be influenced by P2Y12 inhibitor therapy in addition to other risk parameters, including the timing and urgency of the procedure.

Prognostic Value of Baseline Inflammation in Diabetic and Nondiabetic Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: There is a paucity of data on the prognostic value of high-sensitivity C-reactive protein (hsCRP) levels in diabetic and nondiabetic patients undergoing percutaneous coronary intervention (PCI). METHODS: All patients with known baseline hsCRP undergoing PCI at a single tertiary care centre from 2010 to 2017 were included. High hsCRP was defined as > 3 mg/L. Known causes of elevated hsCRP levels and hsCRP > 10 mg/L represented exclusion criteria. The 1-year primary outcome was major adverse cardiovascular events (MACE), including all-cause mortality, myocardial infarction (MI), and target-vessel revascularisation (TVR). RESULTS: Among a total of 11,979 patients included, high hsCRP levels were observed in 24.7% of patients without diabetes and 29.8% of patients with diabetes (P < 0.001). Both diabetics and nondiabetics with high hsCRP levels had increased rates of MACE compared with their counterparts with low hsCRP (diabetics: adjusted hazard ratio [aHR] 1.58, 95% CI 1.27-1.96; nondiabetics: aHR 1.45, 95% CI 1.13-1.86; P interaction = 0.981) primarily driven by increased rates all-cause deaths (diabetics: aHR 2.32, 95% CI 1.42-3.80; nondiabetics: aHR 3.14, 95% CI 1.74-5.65; P interaction = 0.415). Although high hsCRP levels were associated with increased rates of TVR (aHR 1.35, 95% CI 1.04-1.75) and MI (aHR 1.86, 95% CI 1.18-2.93) only in patients with diabetes, no significant interactions were observed between inflammation and diabetes (P interaction = 0.749 and 0.602, respectively). CONCLUSIONS: Patients undergoing PCI with high levels of hsCRP, defined as > 3 mg/L, have worse ischemic outcomes regardless of diabetes status.

Performance of the academic research consortium high-bleeding risk criteria in patients undergoing PCI for acute myocardial infarction.

Patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) are at increased risk for thrombotic and bleeding complications compared to patients with chronic coronary syndrome (CCS). The academic research consortium (ARC) recently suggested a set of criteria to identify patients at high bleeding risk (HBR). We sought to evaluate the performance of the ARC-HBR criteria among patients undergoing PCI according to clinical presentation. We included all consecutive patients undergoing PCI at a tertiary-care center. Patients were deemed at HBR if they fulfilled ≥ 1 major or ≥ 2 minor ARC-HBR criteria. The primary bleeding endpoint was a composite of in-hospital or post-discharge bleeding at 1-year follow-up. Secondary outcomes included all-cause death and myocardial infarction. Out of 6068 patients, 1391 (22.9 %) presented with AMI and were more often at HBR than those with CCS (46.9 % vs. 43.0 %, p = 0.01). HBR patients had a higher risk for the primary bleeding endpoint than non-HBR, irrespective of the clinical indication for PCI (AMI: 19.5 % vs. 5.5 %; HR 3.86, 95 % CI 2.63-5.69; CCS: 6.8 % vs. 2.6 %; HR 2.65, 95 % CI 1.92-3.68; p-interaction = 0.11). Secondary outcomes followed a similar trend. After multivariable adjustment, AMI presentation remained significantly associated with increased risk for bleeding at 1 year (HR 1.64, 95 % CI 1.13-2.38, p = 0.01). The ARC-HBR criterion associated with the highest bleeding risk was severe/end-stage chronic kidney disease in AMI and moderate/severe anemia in CCS. The ARC-HBR framework successfully identified AMI and CCS patients with increased risk for bleeding complications at 1 year post-PCI. Figure prepared with BioRender.

Impact of Sex on the Functional Assessment of Intermediate Coronary Lesions by Instantaneous Wave-Free Ratio.

Sex differences in coronary physiology and in the pathogenesis of coronary artery disease (CAD) have been previously described. Contrasting data have been reported, so far, about the impact of sex on the assessment of the functional significance of intermediate coronary stenoses by fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR). The present study aimed at assessing the sex differences in the results of iFR in a cohort of patients undergoing coronary angiography. METHODS: We included patients undergoing coronary angiography and the functional assessment of intermediate (40 to 70%) coronary lesions in 2 centers. iFR measurement was performed by pressure-recording guidewire and automatically calculated at the core laboratory using the manufacturers' dedicated software. Quantitative parameters of the coronary lesions were calculated by an automatic edge-detection system. Minimal luminal diameter (MLD), reference diameter (RD), percent diameter stenosis, and length of the lesion were measured. Positive iFR was considered for values < 0.90. RESULTS: We included 325 patients undergoing coronary angiography and iFR evaluation of 371 intermediate coronary stenoses, including 20.6% of women. Females were older, displayed lower body weight and hemoglobin, lower rate of active smoking (p < 0.001) and previous PCI (p = 0.04), lower platelet count (p = 0.001) and creatinine (p = 0.02). Systolic blood pressure and heart rate at admission were more elevated in women (p = 0.001 and p = 0.05, respectively). At angiography, multivessel coronary artery disease was more uncommon (p = 0.001) and proximal lesions were more frequently assessed by iFR (p = 0.04). Mean values of iFR did not differ with sex and neither the percentage of positive iFR (19.1% vs 18.8%, p = 0.99, adjusted OR[95%CI] = 0.51[0.18-1.48], p = 0.22). CONCLUSION: Among patients undergoing functional assessment of intermediate coronary lesions by instantaneous wave-free ratio, no impact of sex was observed on the absolute values or the rate of positivity of iFR.