A matter of sex-persistent predictive value of MECKI score prognostic power in men and women with heart failure and reduced ejection fraction: a multicenter study.

Background: A sex-based evaluation of prognosis in heart failure (HF) is lacking. Methods and results: We analyzed the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score registry, which includes HF with reduced ejection fraction (HFrEF) patients. A cross-validation procedure was performed to estimate weights separately for men and women of all MECKI score parameters: left ventricular ejection fraction (LVEF), hemoglobin, kidney function assessed by Modification of Diet in Renal Disease, blood sodium level, ventilation vs. carbon dioxide production slope, and peak oxygen consumption (peakVO2). The primary outcomes were the composite of all-cause mortality, urgent heart transplant, and implant of a left ventricle assist device. The difference in predictive ability between the native and sex recalibrated MECKI (S-MECKI) was calculated using a receiver operating characteristic (ROC) curve at 2 years and a calibration plot. We retrospectively analyzed 7,900 HFrEF patients included in the MECKI score registry (mean age 61 ± 13 years, 6,456 men/1,444 women, mean LVEF 33% ± 10%, mean peakVO2 56.2% ± 17.6% of predicted) with a median follow-up of 4.05 years (range 1.72-7.47). Our results revealed an unadjusted risk of events that was doubled in men compared to women (9.7 vs. 4.1) and a significant difference in weight between the sexes of most of the parameters included in the MECKI score. S-MECKI showed improved risk classification and accuracy (area under the ROC curve: 0.7893 vs. 0.7799, p = 0.02) due to prognostication improvement in the high-risk settings in both sexes (MECKI score >10 in men and >5 in women). Conclusions: S-MECKI, i.e., the recalibrated MECKI according to sex-specific differences, constitutes a further step in the prognostic assessment of patients with severe HFrEF.

Maternal-fetal dyad beyond the phenomenology of pregnancy: from primordial cardiovascular prevention on out, do not miss this boat!

Pregnancy represents a stress test for every woman's cardiovascular (CV) system, and a pre-existing maternal unfavorable cardio-metabolic phenotype can uncover both adverse pregnancy outcomes and the subsequent development of cardiovascular disease (CVD) risk factors during and after pregnancy. Moreover, the maternal cardiac and extracardiac environment can affect offspring's cardiovascular health through a complex mechanism called developmental programming, in which fetal growth can be influenced by maternal conditions. This interaction continues later in life, as adverse developmental programming, along with lifestyle risk factors and genetic predisposition, can exacerbate and accelerate the development of CV risk factors and CVD in childhood and adolescence. The aim of this narrative review is to summarize the latest evidences regarding maternal-fetal dyad and its role on primordial, primary and secondary CV prevention.

Artificial Intelligence Applied to Electrical and Non-Invasive Hemodynamic Markers in Elderly Decompensated Chronic Heart Failure Patients.

OBJECTIVES: The first aim of this study was to assess the predictive power of Tend interval (Te) and non-invasive hemodynamic markers, based on bioimpedance in decompensated chronic heart failure (CHF). The second one was to verify the possible differences in repolarization and hemodynamic data between CHF patients grouped by level of left ventricular ejection fraction (LVEF). Finally, we wanted to check if repolarization and hemodynamic data changed with clinical improvement or worsening in CHF patients. METHODS: Two hundred and forty-three decompensated CHF patients were studied by 5 min ECG recordings to determine the mean and standard deviation (TeSD) of Te (first study). In a subgroup of 129 patients (second study), non-invasive hemodynamic and repolarization data were recorded for further evaluation. RESULTS: Total in-hospital and cardiovascular mortality rates were respectively 19 and 9%. Te was higher in the deceased than in surviving subjects (Te: 120 ± 28 vs. 100 ± 25 ms) and multivariable logistic regression analysis reported that Te was related to an increase of total (χ2: 35.45, odds ratio: 1.03, 95% confidence limit: 1.02-1.05, p < 0.001) and cardiovascular mortality (χ2: 32.58, odds ratio: 1.04, 95% confidence limit: 1.02-1.06, p < 0.001). Subjects with heart failure with reduced ejection fraction (HFrEF) reported higher levels of repolarization and lower non-invasive systolic hemodynamic data in comparison to those with preserved ejection fraction (HFpEF). In the subgroup, patients with the NT-proBNP reduction after therapy showed a lower rate of Te, heart rate, blood pressures, contractility index, and left ventricular ejection time in comparison with the patients without NT-proBNP reduction. CONCLUSION: Electrical signals from ECG and bioimpedance were capable of monitoring the patients with advanced decompensated CHF. These simple, inexpensive, non-invasive, easily repeatable, and transmissible markers could represent a tool to remotely monitor and to intercept the possible worsening of these patients early by machine learning and artificial intelligence tools.

Sex- and gender-related disparities in chest pain syndromes: the feminine mystique of chest pain.

Chest pain syndromes encompass a wide range of different clinical conditions, being coronary artery disease one of the most important and feared aetiology. Sex and gender disparities have been reported in pathophysiology, clinical presentations, diagnostic work-up and outcomes of patients admitted for chest pain. Biological differences in sexual hormones and neurological pain procession pathways have been proposed as contributors to disparities between men and women; however, gender-related disparities in socio-economic and psychological status have emerged as additional factors involved in these conditions. A better understanding of gender- and sex-related disparities will lead to improved clinical care and management of chest pain syndromes in both men and women. In this comprehensive review, we describe the existing knowledge regarding sex and gender-based differences in management and outcomes of chest pain syndromes in order to stimulate and promote the development of a more sex- and gender-oriented approach to these conditions.

The long-term cardiovascular impairment of COVID 19: need for clarity in definition and terminology.

Clinical experience and several large studies in the field have found that SARS-CoV-2 infection can cause long-term persistent cardiovascular (CV) impairment beyond the acute phase of the disease. This has resulted in a major public health concern worldwide. Regarding COVID-related long-term involvement of various organs and systems, using specific definitions and terminology is crucial to point out time relationships, lingering damage, and outcome, mostly when symptoms and signs of CV disease persist beyond the acute phase. Due to a lack of a common standardized definition, investigators have used interchangeable terms such as "long COVID," "post-COVID," or "post-acute sequelae of COVID-19" to describe CV involvement, thus causing some confusion. For the sake of clarity, the aim of this paper is to discuss the definition and terminology used in defining sequelae after the acute phase of COVID-19, thus pointing out the meaning of definitions like acute cardiac injury, post-acute sequelae of COVID-19, long COVID syndrome, and increased risk of atherosclerotic cardiovascular disease.

What about chronotropic incompetence in heart failure with mildly reduced ejection fraction? Clinical and prognostic implications from the Metabolic Exercise combined with Cardiac and Kidney Indexes score dataset.

AIMS: Chronotropic incompetence (CI) is a strong predictor of outcome in heart failure with reduced ejection fraction, however no data on its clinical and prognostic impacts in heart failure with mildly reduced ejection fraction (HFmrEF) are available. Therefore, the study aims to investigate, in a large multicentre HFmrEF cohort, the prevalence of CI as well as its relationship with exercise capacity and its prognostic role over the cardiopulmonary exercise testing (CPET) parameters. METHODS AND RESULTS: Within the Metabolic Exercise combined with Cardiac and Kidney Indexes (MECKI) database, we analysed data of 864 HFmrEF out of 1164 stable outpatients who performed a maximal CPET at the cycle ergometer and who had no significant rhythm disorders or comorbidities. The primary study endpoint was cardiovascular (CV) death. All-cause death was also explored. Chronotropic incompetence prevalence differed depending on the method (peak heart rate, pHR% vs. pHR reserve, pHRR%) and the cut-off adopted (pHR% from ≤75% to ≤60% and pHRR% ≤ 65% to ≤50%), ranging from 11% to 62%. A total of 84 (9.7%) CV deaths were collected, with 39 (4.5%) occurring within 5 years. At multivariate analysis, both pHR% [hazard ratio 0.97 (0.95-0.99), P < 0.05] and pHRR% [hazard ratio 0.977 (0.961-0.993), P < 0.01] were associated with the primary endpoint. A pHR% ≤ 75% and a pHRR% ≤ 50% represented the most accurate cut-off values in predicting the outcome. CONCLUSION: The study suggests an association between blunted exercise-HR response, functional capacity, and CV death risk among patients with HFmrEF. Whether the CI presence might be adopted in daily HFmrEF management needs to be addressed in larger prospective studies.

Chronotropic incompetence is an easy-to-obtain additive parameter for cardiovascular death risk stratification in heart failure with mildly reduced ejection fraction (HFmrEF). Peak heart rate and peak heart rate reserve are associated with exercise capacity in HFmrEF. Peak heart rate and peak heart rate reserve are associated with cardiovascular death in HFmrEF.

Determinants of exercise performance in heart failure patients with extremely reduced cardiac output and left ventricular assist device.

The evaluation of exercise capacity and cardiac output (QC) is fundamental in the management of patients with advanced heart failure (AdHF). QC and peak oxygen uptake (VO2) have a pivotal role in the prognostic stratification and in the definition of therapeutic interventions, including medical therapies and devices, but also specific treatments such as heart transplantation and left ventricular assist device (LVAD) implantation. Due to the intertwined relationship between exercise capacity and daily activities, exercise intolerance dramatically has impact on the quality of life of patients. It is a multifactorial process that includes alterations in central and peripheral haemodynamic regulation, anaemia and iron deficiency, pulmonary congestion, pulmonary hypertension, and peripheral O2 extraction. This paper aims to review the pathophysiological background of exercise limitations in HF patients and to examine the complex physiology of exercise in LVAD recipients, analysing the interactions between the cardiopulmonary system, the musculoskeletal system, the autonomic nervous system, and the pump. We performed a literature review to highlight the current knowledge on this topic and possible interventions that can be implemented to increase exercise capacity in AdHF patients-including administration of levosimendan, rehabilitation, and the intriguing field of LVAD speed changes. The present paper confirms the role of CPET in the follow-up of this peculiar population and the impact of exercise capacity on the quality of life of AdHF patients.

Heart failure patients with improved ejection fraction: Insights from the MECKI score database.

AIMS: Improvement of left ventricular ejection fraction is a major goal of heart failure (HF) treatment. However, data on clinical characteristics, exercise performance and prognosis in HF patients who improved ejection fraction (HFimpEF) are scarce. The study aimed to determine whether HFimpEF patients have a distinct clinical phenotype, biology and prognosis than HF patients with persistently reduced ejection fraction (pHFrEF). METHODS AND RESULTS: A total of 7948 patients enrolled in the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score database were evaluated (median follow-up of 1490 days). We analysed clinical, laboratory, electrocardiographic, echocardiographic, exercise, and survival data from HFimpEF (n = 1504) and pHFrEF (n = 6017) patients. The primary endpoint of the study was the composite of cardiovascular death, left ventricular assist device implantation, and urgent heart transplantation. HFimpEF patients had lower HF severity: left ventricular ejection fraction 44.0 [41.0-47.0] versus 29.7 [24.1-34.5]%, B-type natriuretic peptide 122 [65-296] versus 373 [152-888] pg/ml, haemoglobin 13.5 [12.2-14.6] versus 13.7 [12.5-14.7] g/dl, renal function by the Modification of Diet in Renal Disease equation 72.0 [56.7-89.3] versus 70.4 [54.5-85.3] ml/min, peak oxygen uptake 62.2 [50.7-74.1] versus 52.6 [41.8-64.3]% predicted, minute ventilation-to-carbon dioxide output slope 30.0 [26.9-34.4] versus 32.1 [28.0-38.0] in HFimpEF and pHFrEF, respectively (p < 0.001 for all). Cardiovascular mortality rates were 26.6 and 46.9 per 1000 person-years for HFimpEF and pHFrEF, respectively (p < 0.001). Kaplan-Meier analysis showed that HFimpEF had better a long-term prognosis compared with pHFrEF patients. After adjustment for variables differentiating HFimpEF from pHFrEF, except echocardiographic parameters, the Kaplan-Meier curves showed the same prognosis. CONCLUSIONS: Heart failure with improved ejection fraction represents a peculiar group of HF patients whose clinical, laboratory, electrocardiographic, echocardiographic, and exercise characteristics parallel the recovery of systolic function. Nonetheless, these patients remain at risk for adverse outcome.

Effect of Head-Up/-Down Tilt on ECG Segments and Myocardial Temporal Dispersion in Healthy Subjects.

The head-up/-down tilt test acutely modifies the autonomic nervous system balance throughout a deactivation of the cardiopulmonary reflexes. The present study examines the influence of head-up/-down tilt on a number of ECG segments. A total of 20 healthy subjects underwent a 5 min ECG and noninvasive hemodynamic bio-impedance recording, during free and controlled breathing, lying at (a) 0°; (b) -45°, tilting up at 45°, and tilting up at 90°. Heart rate variability power spectral analysis was obtained throughout some ECG intervals: P-P (P), P-Q (PQ), PeQ (from the end of P to Q wave), Q-R peak (QR intervals), Q-R-S (QRS), Q-T peak (QTp), Q-T end (QTe), STp, STe, T peak-T end (Te), and, eventually, the TeP segments (from the end of T to the next P waves). Results: In all study conditions, the Low Frequency/High FrequencyPP and LFPP normalized units (nu) were significantly lower than the LF/HFRR and LFRRnu, respectively. Conversely, the HFPP and HFPPnu were significantly higher in all study conditions. STe, QTp, and QTe were significantly related to the PP and RR intervals, whereas the T wave amplitude was inversely related to the standard deviations of all the myocardial repolarization variables and to the left ventricular end-systolic volume (LVEDV). The T wave amplitude diminished during head-up tilt and significantly correlated with the LVEDV.

Sex Differences in Repolarization Markers: Telemonitoring for Chronic Heart Failure Patients.

Aging and chronic heart failure (CHF) are responsible for the temporal inhomogeneity of the electrocardiogram (ECG) repolarization phase. Recently, some short period repolarization-dispersion parameters have been proposed as markers of acute decompensation and of mortality risk in CHF patients. Some important differences in repolarization between sexes are known, but their impact on ECG markers remains unstudied. The aim of this study was to evaluate possible differences between men and women in ECG repolarization markers for the telemonitoring of CHF patients. METHOD: 5 min ECG recordings were collected to assess the mean and standard deviation (SD) of the following variables: QT end (QTe), QT peak (QTp), and T peak to T end (Te) in 215 decompensated CHF (age range: from 49 to 103 years). Thirty-day mortality and high levels of NT-pro BNP (<75 percentile) were considered markers of decompensated CHF. RESULTS: A total of 34 patients (16%) died during the 30-day follow-up, without differences between sexes. Women showed a more preserved ejection fraction and higher LDL and total cholesterol levels. Among female patients, implantable cardioverter devices, statins, and antiplatelet agents were less used. Data for Te mean showed increased values among deceased men and women compared to survival, but TeSD was shown to be the most reliable marker for CHF reacutization in both sexes. CONCLUSION: TeSD could be considered a risk factor for CHF worsening and complications for female and male patients, but different cut offs should be taken into account. (ClinicalTrials.gov number, NCT04127162.).

The Impact of Physical Activity and Inactivity on Cardiovascular Risk across Women's Lifespan: An Updated Review.

Physical inactivity (PI) represents a significant, modifiable risk factor that is more frequent and severe in the female population worldwide for all age groups. The physical activity (PA) gender gap begins early in life and leads to considerable short-term and long-term adverse effects on health outcomes, especially cardiovascular (CV) health. Our review aims to highlight the prevalence and mechanisms of PI across women's lifespan, describing the beneficial effects of PA in many physiological and pathological clinical scenarios and underlining the need for more awareness and global commitment to promote strategies to bridge the PA gender gap and limit PI in current and future female generations.

Cardiopulmonary exercise testing and heart failure: a tale born from oxygen uptake.

Since 50 years, cardiopulmonary exercise testing (CPET) plays a central role in heart failure (HF) assessment. Oxygen uptake (VO2) is one of the main HF prognostic indicators, then paralleled by ventilation to carbon dioxide (VE/VCO2) relationship slope. Also anaerobic threshold retains a strong prognostic power in severe HF, especially if expressed as a percent of maximal VO2 predicted value. Moving beyond its absolute value, a modern approach is to consider the percentage of predicted value for peak VO2 and VE/VCO2 slope, thus allowing a better comparison between genders, ages, and races. Several VO2 equations have been adopted to predict peak VO2, built considering different populations. A step forward was made possible by the introduction of reliable non-invasive methods able to calculate cardiac output during exercise: the inert gas rebreathing method and the thoracic electrical bioimpedance. These techniques made possible to calculate the artero-venous oxygen content differences (ΔC(a-v)O2), a value related to haemoglobin concentration, pO2, muscle perfusion, and oxygen extraction. The role of haemoglobin, frequently neglected, is however essential being anaemia a frequent HF comorbidity. Finally, peak VO2 is traditionally obtained in a laboratory setting while performing a standardized physical effort. Recently, different wearable ergo-spirometers have been developed to allow an accurate metabolic data collection during different activities that better reproduce HF patients' everyday life. The evaluation of exercise performance is now part of the holistic approach to the HF syndrome, with the inclusion of CPET data into multiparametric prognostic scores, such as the MECKI score.

Cardiovascular prevention in women: an update by the Italian Society of Cardiology working group on 'Prevention, hypertension and peripheral disease'.

The recent pandemic has substantially changed the approach to the prevention of cardiovascular diseases in women. Women have been significantly impacted by the changes that occurred during the pandemic and the quarantine adopted to prevent the spread of the disease. Changes involved prevention both through the reduction of visits and preventive screening and through social and economic changes. It is necessary to adopt new cardiovascular prevention approaches focused on returning to healthy lifestyles, reducing stress and depression also using modern tools such as telemedicine, mobile phone applications and the web. These tools convey messages in a persuasive way especially in young and adult women. There is less impact of these new tools on older women towards whom it is important to adopt a more traditional approach. This review focuses on the new approach to cardiovascular prevention in women in light of the lifestyle changes recorded during the pandemic and which led to an increase in obesity examines the effects on the cardiovascular system induced by stress and depression and analyses the new high blood pressure guidelines and indications that are specific to women.

Influence of exertional oscillatory breathing and its temporal behavior in patients with heart failure and reduced ejection fraction.

BACKGROUND: Exertional oscillatory breathing (EOV) represents an emerging prognostic marker in heart failure (HF) patients, however little is known about EOV meaning with respect to its disappearance/persistence during cardiopulmonary exercise test (CPET). The present single-center study evaluated EOV clinical and prognostic impact in a large cohort of reduced ejection fraction HF patients (HFrEF) and, contextually, if a specific EOV temporal behavior might be an addictive risk predictor. METHODS AND RESULTS: Data from 1.866 HFrEF patients on optimized medical therapy were analysed. The primary cardiovascular (CV) study end-point was cardiovascular death, heart transplantation or LV assistance device (LVAD) implantation at 5-years. For completeness a secondary end-point of total mortality at 5- years was also explored. EOV presence was identified in 251 patients (13%): 142 characterized by EOV early cessation (Group A) and 109 by EOV persistence during the whole CPET (Group B). The entire EOV Group showed worse clinical and functional status than NoEOV Group (n = 1.615) and, within the EOV Group, Group B was characterized by a more severe HF. At CV survival analysis, EOV patients showed a poorer outcome than the NoEOV Group (events 27.1% versus 13.1%, p < 0.001) both unpolished and after matching for main confounders. Instead, no significant differences were found between EOV Group A and B with respect to CV outcome. Conversely the analysis for total mortality failed to be significant. CONCLUSIONS: Our analysis, albeit retrospective, supports the inclusion of EOV into a CPET-centered clinical and prognostic evaluation of the HFrEF patients. EOV characterizes per se a more advanced HFrEF stage with an unfavorable CV outcome. However, the EOV persistence, albeit suggestive of a more severe HF, does not emerge as a further prognostic marker.

Electrocardiographic and other Noninvasive Hemodynamic Markers in Decompensated CHF Patients.

Acutely decompensated chronic heart failure (adCHF) is among the most important causes of in-hospital mortality. R-wave peak time (RpT) or delayed intrinsicoid deflection was proposed as a risk marker of sudden cardiac death and heart failure decompensation. Authors want to verify if QR interval or RpT, obtained from 12-lead standard ECG and during 5-min ECG recordings (II lead), could be useful to identify adCHF. At hospital admission, patients underwent 5-min ECG recordings, obtaining mean and standard deviation (SD) of the following ECG intervals: QR, QRS, QT, JT, and T peak-T end (Te). The RpT from a standard ECG was calculated. Patients were grouped by the age-stratified Januzzi NT-proBNP cut-off. A total of 140 patients with suspected adCHF were enrolled: 87 (mean age 83 ± 10, M/F 38/49) with and 53 (mean age: 83 ± 9, M/F: 23/30) without adCHF. V5-, V6- (p < 0.05) RpT, and QRSD, QRSSD, QTSD, JTSD, and TeSDp < 0.001 were significantly higher in the adCHF group. Multivariable logistic regression analysis demonstrated that the mean of QT (p < 0.05) and Te (p < 0.05) were the most reliable markers of in-hospital mortality. V6 RpT was directly related to NT-proBNP (r: 0.26, p < 0.001) and inversely related to a left ventricular ejection fraction (r: 0.38, p < 0.001). The intrinsicoid deflection time (obtained from V5-6 and QRSD) could be used as a possible marker of adCHF.

Impact of COVID-19 on the cardiovascular health of women: a review by the Italian Society of Cardiology Working Group on 'gender cardiovascular diseases'.

The coronavirus disease 19 (COVID-19), due to coronavirus 2 (SARS-CoV-2) infection, presents with an extremely heterogeneous spectrum of symptoms and signs. COVID-19 susceptibility and mortality show a significant sex imbalance, with men being more prone to infection and showing a higher rate of hospitalization and mortality than women. In particular, cardiovascular diseases (preexistent or arising upon infection) play a central role in COVID-19 outcomes, differently in men and women. This review will discuss the potential mechanisms accounting for sex/gender influence in vulnerability to COVID-19. Such variability can be ascribed to both sex-related biological factors and sex-related behavioural traits. Sex differences in cardiovascular disease and COVID-19 involve the endothelial dysfunction, the innate immune system and the renin-angiotensin system (RAS). Furthermore, the angiotensin-converting enzyme 2 (ACE2) is involved in disease pathogenesis in cardiovascular disease and COVID-19 and it shows hormone-dependent actions. The incidence of myocardial injury during COVID-19 is sex-dependent, predominantly in association with a greater degree of inflammation and coagulation disorders among men. Its pathogenesis is not fully elucidated, but the main theories foresee a direct role for the ACE2 receptor, the hyperimmune response and the RAS imbalance, which may also lead to isolated presentation of COVID-19-mediated myopericarditis. Moreover, the latest evidence on cardiovascular diseases and their relationship with COVID-19 during pregnancy will be discussed. Finally, authors will analyse the prevalence of the long-covid syndrome between the two sexes and its impact on the quality of life and cardiovascular health.

The importance of re-evaluating the risk score in heart failure patients: An analysis from the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score database.

BACKGROUND: The role of risk scores in heart failure (HF) management has been highlighted by international guidelines. In contrast with HF, which is intrinsically a dynamic and unstable syndrome, all its prognostic studies have been based on a single evaluation. We investigated whether time-related changes of a well-recognized risk score, the MECKI score, added prognostic value. MECKI score is based on peak VO2, VE/VCO2 slope, Na+, LVEF, MDRD and Hb. METHODS: A multi-centre retrospective study was conducted involving 660 patients who performed MECKI re-evaluation at least 6 months apart. Based on the difference between II and I evaluation of MECKI values (MECKI II - MECKI I = ∆ MECKI) the study population was divided in 2 groups: those presenting a score reduction (∆ MECKI <0, i.e. clinical improvement), vs. patients presenting an increase (∆ MECKI >0, clinical deterioration). RESULTS: The prognostic value of MECKI score is confirmed also when re-assessed during follow-up. The group with improved MECKI (366 patients) showed a better prognosis compared to patients with worsened MECKI (294 patients) (p < 0.0001). At 1st evaluation, the two groups differentiated by LVEF, VE/VCO2 slope and blood Na+ concentration, while at 2nd evaluation they differentiated in all 6 parameters considered in the score. The patients who improved MECKI score, improved in all components of the score but hemoglobin, while patients who worsened the score, worsened all parameters. CONCLUSIONS: This study shows that re-assessment of MECKI score identifies HF subjects at higher risk and that score improvement or deterioration regards several MECKI score generating parameters confirming the holistic background of HF.

Gender Differences and Cardiometabolic Risk: The Importance of the Risk Factors.

Metabolic syndrome (Mets) is a clinical condition characterized by a cluster of major risk factors for cardiovascular disease (CVD) and type 2 diabetes: proatherogenic dyslipidemia, elevated blood pressure, dysglycemia, and abdominal obesity. Each risk factor has an independent effect, but, when aggregated, they become synergistic, doubling the risk of developing cardiovascular diseases and causing a 1.5-fold increase in all-cause mortality. We will highlight gender differences in the epidemiology, etiology, pathophysiology, and clinical expression of the aforementioned Mets components. Moreover, we will discuss gender differences in new biochemical markers of metabolic syndrome and cardiovascular risk.

Does moderate hyperkalemia influence survival in HF? Insights from the MECKI score data base.

BACKGROUND: The prognostic role of moderate hyperkalemia in reduced ejection fraction (HFrEF) patients is still controversial. Despite this, it affects the use of renin-angiotensin-aldosterone system inhibitors (RAASi) with therapy down-titration or discontinuation. OBJECTIVES: Aim of the study was to assess the prognostic impact of moderate hyperkalemia in chronic HFrEF optimally treated patients. METHODS AND RESULTS: We retrospectively analyzed MECKI (Metabolic Exercise test data combined with Cardiac and Kidney Indexes) database, with median follow-up of 4.2 [IQR 1.9-7.5] years. Data on K+ levels were available in 7087 cases. Patients with K+ plasma level ≥ 5.6 mEq/L and < 4 mEq/L were excluded. Remaining patients were categorized into normal >4 and < 5 mEq/L (n = 4826, 68%) and moderately high ≥5.0 and ≤ 5.5 mEq/L (n = 496, 7%) K+. Then patients were matched by propensity score in 484 couplets of patients. MECKI score value was 7% [IQR 3.1-14.1%] and 7.3% [IQR 3.4-15%] (p = 0.678) in patients with normal and moderately high K+ values while cardiovascular mortality events at two years follow-up were 41 (4.2%) and 33 (3.4%) (p = 0.333) in each group respectively. CONCLUSIONS: Moderate hyperkalemia does not influence patients' outcome in a large cohort of ambulatory HFrEF patients.