Role of frailty on cardiac rehabilitation in hospitalized older patients.

BACKGROUND: Cardiovascular diseases are the leading cause of mortality, morbidity, and disability in the world, especially in the older adults. A relevant proportion of patients admitted to Cardiac Rehabilitation (CR) may suffer from frailty, a complex geriatric syndrome with multifactorial aetiology. AIMS: The hypothesis underlying the study is that frailty complicates the management of older patients undergoing CR. The main objective is, therefore, to determine the relationship between frailty and CR outcomes in hospitalized older adults. METHODS: The participants have been recruited among patients aged ≥ 65 years admitted at the hospital for CR. A Comprehensive Geriatric Assessment (CGA)-based Frailty Index (FI) was created following a standard procedure. The outcome was measured as the ratio between 6-min walk test (6MWT) distance at the end of CR and normal predicted values for a healthy adult of same age and gender, according to reference equations. RESULTS: The study population consisted of 559 elderly patients, 387 males (69.2%), with age of 72 (69-76) years. The most frequent diagnosis at admission was ischaemic heart disease (231, 41.5%) and overall 6MWT ratio was 0.62 ± 0.21. At the multivariable regression analysis, gender, diagnosis and FI were significantly and independently associated with 6MWT ratio (p ≤ 0.0001, p ≤ 0.001 and p ≤ 0.0001, respectively), while no significant association emerged for age. CONCLUSION: FI resulted independently correlated to 6MWT ratio in a population of older patients undergoing in-hospital CR programs. Frailty is a multifactorial geriatric syndrome whose assessment is essential for prognostic evaluation of older patients, also in CR clinical setting.

Impact of body mass index on cardiac adrenergic derangement in heart failure patients: a 123I-mIBG imaging study.

PURPOSE: To assess the impact of body mass index (BMI) on cardiac adrenergic derangement, measured by iodine-123 meta-iodobenzylguanidine (123I-mIBG) imaging in heart failure (HF) patients. Overweight and obesity represent relevant health issues, and augmented sympathetic tone has been described in patients with increased BMI. An extensive literature supports that HF-dependent cardiac denervation, measured through mIBG parameters, is an independent predictor of cardiovascular outcomes and mortality. However, the influence of BMI on cardiac mIBG uptake has not been largely investigated. METHODS: We prospectively enrolled patients with systolic HF, collecting demographic, clinical, echocardiographic data, and mIBG imaging parameters. In order to detect the factors associated with mIBG parameters, a model building strategy, based on the Multivariable Fractional Polynomial algorithm, has been employed. RESULTS: We studied 249 patients with systolic HF, mean age of 66.4 ± 10.6 years, and mean left ventricular ejection fraction (LVEF) of 30.7% ± 6.4, undergoing cardiac 123I-mIBG imaging to assess HF severity and prognosis. Seventy-eight patients (31.3%) presented a BMI ≥ 30 kg/m2 and obese patients showed a significant reduction in early heart to mediastinum (H/M) ratio (1.66 ± 0.19 vs. 1.75 ± 0.26; p = 0.008) and a trend to reduction in washout rate (33.6 ± 18.3 vs. 38.1 ± 20.1; p = 0.092) compared with patients with BMI < 30 kg/m2. Multiple regression analysis revealed that BMI, age, and LVEF were significantly correlated with early and late H/M ratios. CONCLUSIONS: Results of the present study indicate that BMI, together with LVEF and age, is independently correlated with cardiac mIBG uptake in HF patients.

Clinical application of nasal nitric oxide measurement in allergic rhinitis: A systematic review and meta-analysis.

BACKGROUND: Nasal nitric oxide (nNO) is considered a biomarker of nasal inflammation. OBJECTIVE: To perform a systematic review with meta-analysis and meta-regressions on the association between nNO levels and allergic rhinitis (AR). METHODS: PubMed, Web of Science, Scopus, and EMBASE databases were systematically searched. Differences between cases and controls were expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). RESULTS: Overall, 39 articles were included: 30 containing data on nNO measured by nasal aspiration (1881 patients with AR and 1337 controls) and 12 assessing nNO by nasal exhalation (525 patients with AR and 350 controls). Compared with controls, AR presented significantly higher nNO values both during nasal aspiration (SMD, 1.309; 95% CI, 0.841-1.777; P < .001) and nasal exhalation (SMD, 0.708; 95% CI, 0.303-1.114; P = .001). Sensitivity and subgroup analyses confirmed that the results for the evaluated outcomes were not affected by the presence of clinical confounding factors (asthma, nasal polyps, inhaled corticosteroids, smoking history), this being valid for both perennial and seasonal diseases during exposure to allergens. For the aspiration method, meta-regressions indicated that older age and a better pulmonary function were associated with a lower difference in nNO levels between patients with AR and controls, whereas an increasing aspiration flow was associated with a high effect size. CONCLUSION: nNO levels are higher in AR, particularly when using high aspiration flows and in younger patients, who often perceive this condition as a source of disability. Further studies are needed to evaluate the usefulness of this biomarker for monitoring airway disorders and optimizing strategies in different settings (community, hospital, rehabilitation).

Validation of the echocardiographic assessment of epicardial adipose tissue thickness at the Rindfleisch fold for the prediction of coronary artery disease.

BACKGROUND AND AIM: Echocardiography is a promising technique for the assessment of epicardial adipose tissue (EAT). Increased EAT thickness is associated with different cardiac diseases, including; coronary artery disease (CAD). Since several different echocardiographic approaches have been proposed to measure EAT, the identification of a standardized method is needed. We propose the assessment of EAT maximal thickness at the Rindfleisch fold, the reproducibility of this measurement and its correlation with EAT thickness and volume assessed at cardiac magnetic resonance (CMR). Finally, we will test the predictive role of this measurement on the presence of significant CAD. METHODS AND RESULTS: In 1061 patients undergoing echocardiography, EAT thickness was measured at the level of the Rindfleisch fold. In 70 patients, we tested the relationship between echo-EAT thickness and EAT thickness and volume assessed at CMR. In 499 patients with suspected CAD, undergoing coronary artery angiography, we tested the predictive value of EAT on the presence of significant CAD. Echo-EAT thickness measurements had an excellent reliability as indicated by the inter-observer (ICC:0.97; 95% C.I. 0.96 to 0.98) and intra-observer (ICC:0.99; 95% C.I. 0.98 to 0.99) reliability rates. Echo-EAT thickness significantly correlated with CMR-EAT thickness and volume (p < 0.001). An EAT thickness value >10 mm discriminated patients with significant CAD at coronary angiography (p < 0.001). At multivariable analysis, including demographic data and cardiovascular risk factors, EAT thickness was an independent predictor of significant CAD and showed an additive predictive value over common atherosclerotic risk factors. CONCLUSIONS: Echocardiographic assessment of EAT thickness at the level of the Rindfleisch fold represents a simple and trustworthy method. An increased EAT thickness shows an additive predictive value on CAD over common atherosclerotic risk factors, thus suggesting its potential clinical use for CAD risk stratification.

Impact of aging on cardiac sympathetic innervation measured by 123I-mIBG imaging in patients with systolic heart failure.

PURPOSE: Sympathetic nervous system (SNS) hyperactivity is a salient characteristic of chronic heart failure (HF) and contributes to the progression of the disease. Iodine-123 meta-iodobenzylguanidine (123I-mIBG) imaging has been successfully used to assess cardiac SNS activity in HF patients and to predict prognosis. Importantly, SNS hyperactivity characterizes also physiological ageing, and there is conflicting evidence on cardiac 123I-mIBG uptake in healthy elderly subjects compared to adults. However, little data are available on the impact of ageing on cardiac sympathetic nerve activity assessed by 123I-mIBG scintigraphy, in patients with HF. METHODS AND RESULTS: We studied 180 HF patients (age = 66.1 ± 10.5 years [yrs]), left ventricular ejection fraction (LVEF = 30.6 ± 6.3 %) undergoing cardiac 123I-mIBG imaging. Early and late heart to mediastinum (H/M) ratios and washout rate were calculated in all patients. Demographic, clinical, and echocardiographic data were also collected. Our study population consisted of 53 patients aged >75 years (age = 77.7 ± 4.0 year), 67 patients aged 62-72 years (age = 67.9 ± 3.2 years) and 60 patients aged ≤61 year (age = 53.9 ± 5.6 years). In elderly patients, both early and late H/M ratios were significantly lower compared to younger patients (p < 0.05). By multivariate analysis, H/M ratios (both early and late) and washout rate were significantly correlated with LVEF and age. CONCLUSIONS: Our data indicate that, in a population of HF patients, there is an independent age-related effect on cardiac SNS innervation assessed by 123I-mIBG imaging. This finding suggests that cardiac 123I-mIBG uptake in patients with HF might be affected by patient age.

Impact of diabetes mellitus on lymphocyte GRK2 protein levels in patients with heart failure.

BACKGROUND: Diabetes mellitus (DM) is associated with impaired prognosis in patients with heart failure (HF), but pathogenic mechanisms are unclear. In the failing heart, elevated ß-adrenergic receptor (ß-AR) activation by catecholamines causes G-protein-coupled receptor kinase-2 (GRK2) upregulation which is responsible for ß-AR signalling dysfunction. Importantly, GRK2 expression, measured in peripheral lymphocytes of HF patients, correlates with levels of this kinase in the failing myocardium reflecting the loss of hemodynamic function. Moreover, HF-related GRK2 protein overexpression promotes insulin resistance by interfering with insulin signalling. The aim of this study was to assess lymphocyte GRK2 protein levels in HF patients with and without DM. METHODS AND MATERIALS: Patients with a diagnosis of HF were enrolled in the study. All subjects underwent a complete clinical examination (including NYHA functional class assessment and echocardiography) and blood draw for serum N-terminal pro-brain natriuretic peptide (NT-proBNP), lymphocyte GRK2 and plasma norepinephrine (NE) levels. Demographic data including age, sex, medications, cardiovascular risk factors and presence of comorbidities were also collected. RESULTS: Two hundred and sixty-eight patients with HF (left ventricular ejection fraction [LVEF] 30.6 ± 7.6%) with and without DM were enrolled. No differences between the two groups were found in terms of demography, HF aetiology, LVEF, NYHA class, NE and NT-proBNP. GRK2 was significantly higher in patients with DM compared to non-DM. At multivariate linear regression analysis, LVEF, NE, NT-proBNP and diabetes came out to be independent predictors of GRK2 levels in the overall study population. CONCLUSION: In HF patients, DM is associated with significantly more elevated lymphocyte GRK2 protein levels, likely reflecting more compromised cardiac ß-AR signalling/function, despite similar hemodynamic status and neuro-hormonal activation compared to patients without DM. These findings contribute to explain the negative prognostic impact of DM in patients with HF.

Alterations of left ventricular deformation and cardiac sympathetic derangement in patients with systolic heart failure: a 3D speckle tracking echocardiography and cardiac ¹²³I-MIBG study.

PURPOSE: Myocardial contractile function is under the control of cardiac sympathetic activity. Three-dimensional speckle tracking echocardiography (3D-STE) and cardiac imaging with (123)I-metaiodobenzylguanidine ((123)I-MIBG) are two sophisticated techniques for the assessment of left ventricular (LV) deformation and sympathetic innervation, respectively, which offer important prognostic information in patients with heart failure (HF). The purpose of this investigation was to explore, in patients with systolic HF, the relationship between LV deformation assessed by 3D-STE and cardiac sympathetic derangement evaluated by (123)I-MIBG imaging. METHODS: We prospectively studied 75 patients with systolic HF. All patients underwent a 3D-STE study (longitudinal, circumferential, area and radial) and (123)I-MIBG planar and SPECT cardiac imaging. RESULTS: 3D-STE longitudinal, circumferential and area strain values were correlated with (123)I-MIBG late heart to mediastinum (H/M) ratio and late SPECT total defect score. After stratification of the patients according to ischaemic or nonischaemic HF aetiology, we observed a good correlation of all 3D-STE measurements with late H/M ratio and SPECT data in the ischaemic group, but in patients with HF of nonischaemic aetiology, no correlation was found between LV deformation and cardiac sympathetic activity. At the regional level, the strongest correlation between LV deformation and adrenergic innervation was found for the left anterior descending coronary artery distribution territory for all four 3D-STE values. In multivariate linear regression analyses, including age, gender, LV ejection fraction, NYHA class, body mass index, heart rate and HF aetiology, only 3D-STE area and radial strain values significantly predicted cardiac sympathetic derangement on (123)I-MIBG late SPECT. CONCLUSION: This study indicated that 3D-STE measurements are correlated with (123)I-MIBG planar and SPECT data. Furthermore, 3D-STE area and radial strain values, but not LVEF, predict cardiac sympathetic derangement in human postischaemic HF.

Endotyping Chronic Respiratory Diseases: T2 Inflammation in the United Airways Model.

Over the past 15 years, the paradigm of viewing the upper and lower airways as a unified system has progressively shifted the approach to chronic respiratory diseases (CRDs). As the global prevalence of CRDs continues to increase, it becomes evident that acknowledging the presence of airway pathology as an integrated entity could profoundly impact healthcare resource allocation and guide the implementation of pharmacological and rehabilitation strategies. In the era of precision medicine, endotyping has emerged as another novel approach to CRDs, whereby pathologies are categorized into distinct subtypes based on specific molecular mechanisms. This has contributed to the growing acknowledgment of a group of conditions that, in both the upper and lower airways, share a common type 2 (T2) inflammatory signature. These diverse pathologies, ranging from allergic rhinitis to severe asthma, frequently coexist and share diagnostic and prognostic biomarkers, as well as therapeutic strategies targeting common molecular pathways. Thus, T2 inflammation may serve as a unifying endotypic trait for the upper and lower airways, reinforcing the practical significance of the united airways model. This review aims to summarize the literature on the role of T2 inflammation in major CRDs, emphasizing the value of common biomarkers and integrated treatment strategies targeting shared molecular mechanisms.

Implementing Translational Research to Understand the Future of COVID-19 and Its Long-Term Consequences: A Degrowth Perspective or the Transformation of a Global Emergency?

It has now been three years since the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first gave rise to a global health crisis [...].

Cardiac and Pulmonary Rehabilitation: Two Underutilized Approaches with Some Unexpected Benefits.

Although still underutilized [...].

Pulmonary rehabilitation and endothelial function in patients with chronic obstructive pulmonary disease: A prospective cohort study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with subclinical atherosclerosis and endothelial dysfunction, thereby leading to increased cardiovascular risk. In the present study, we evaluated the changes in endothelium-dependent flow-mediated dilation (FMD) in a cohort of severe COPD patients undergoing pulmonary rehabilitation. METHODS: Consecutive COPD patients referred to our Pulmonary Rehabilitation Unit were screened for inclusion. All study procedures were performed at hospital admission and discharge. RESULTS: Of 78 patients screened for eligibility, a total of 40 participants (67.5% males, median age 72.5 years) were included. After pulmonary rehabilitation, a significant improvement in functional parameters, exercise capacity, and measures of disability and quality of life were documented. FMD changed from 3.25% (IQR: 2.31-4.26) to 4.95% (IQR: 3.57-6.02), corresponding to a 52.3% increase of its median value (P < 0.001). Significantly lower changes in FMD were documented in COPD patients with hypercholesterolemia as compared to those without (+0.33% ± 1.61 vs. +1.62% ± 1.59, P = 0.037). Changes in FMD (ΔFMD) were positively associated with changes in forced expiratory volume in 1 s (FEV1), when expressed both as absolute values (ΔFEV1) (r = 0.503, P = 0.002) and as percentages of predicted values (ΔFEV1%) (r = 0.608; P < 0.001). In multiple linear regressions, after adjusting for major cardiovascular risk factors, ΔFEV1 (ß=0.342; P = 0.049) and ΔFEV1% (ß=0.480; P = 0.015) were both confirmed as independent predictors of ΔFMD. CONCLUSIONS: Results of our study suggest that endothelial function may improve in COPD after pulmonary rehabilitation. The potential beneficial effect in terms of cardiovascular risk prevention should be evaluated in ad hoc designed studies.

[Endothelial dysfunction in type 2 diabetic patients with normal coronary arteries. A peripheral arterial tonometry study]. / Evidenza di disfunzione endoteliale in pazienti diabetici di tipo 2 con arterie coronariche angiograficamente normali. Studio con tonometria arteriosa digitale.

AIM: to evaluate endothelial function (EF) in diabetic and non-diabetic patients without CAD by peripheral artery tonometry (PAT) technique. METHODS: a cohort of 94 patients (55 men and 39 postmenopausal women; mean age 63 +/- 9 years) undergoing coronary angiography was divided into 2 groups: 58 patients with DM and (group 1) and 36 patients without DM. Endothelial dysfunction (ED) was assessed by digital pulse amplitude, using a fingertip peripheral arterial tonometry (PAT). As a measure of ED, reactive hyperemia index (RHI) was calculated as the ratio of the digital pulse volume during reactive hyperemia following 5 min ischemia and its basal value. RESULTS: prevalence of cardiovascular risk factors was similar between the two groups. RHI values were significantly lower in diabetic patients compared to non-diabetics (1.72 +/- 0.34 vs 2.00 +/- 0.44; p < 0.005) and they correlated with levels of glycosylated hemoglobin (p = 0.05; r = -0.266). CONCLUSION: despite similar level of other risk factors, EF was much more impaired in diabetic patients than in non-diabetics. These evidences further support the impact of DM on cardiovascular risk.

Cardiopulmonary Exercise Performance and Endothelial Function in Convalescent COVID-19 Patients.

BACKGROUND: Endothelial dysfunction has been proposed as the common pathogenic background of most manifestations of coronavirus disease 2019 (COVID-19). Among these, some authors also reported an impaired exercise response during cardiopulmonary exercise testing (CPET). We aimed to explore the potential association between endothelial dysfunction and the reduced CPET performance in COVID-19 survivors. METHODS: 36 consecutive COVID-19 survivors underwent symptom-limited incremental CPET and assessment of endothelium-dependent flow-mediate dilation (FMD) according to standardized protocols. RESULTS: A significantly higher FMD was documented in patients with a preserved, as compared to those with a reduced, exercise capacity (4.11% ± 2.08 vs. 2.54% ± 1.85, p = 0.048), confirmed in a multivariate analysis (ß = 0.899, p = 0.038). In the overall study population, FMD values showed a significant Pearson's correlation with two primary CPET parameters, namely ventilation/carbon dioxide production (VE/VCO2) slope (r = -0.371, p = 0.026) and end-tidal carbon dioxide tension (PETCO2) at peak (r = 0.439, p = 0.007). In multiple linear regressions, FMD was the only independent predictor of VE/VCO2 slope (ß = -1.308, p = 0.029) and peak PETCO2 values (ß = 0.779, p = 0.021). Accordingly, when stratifying our study population based on their ventilatory efficiency, patients with a ventilatory class III-IV (VE/VCO2 slope ≥ 36) exhibited significantly lower FMD values as compared to those with a ventilatory class I-II. CONCLUSIONS: The alteration of endothelial barrier properties in systemic and pulmonary circulation may represent a key pathogenic mechanism of the reduced CPET performance in COVID-19 survivors. Personalized pharmacological and rehabilitation strategies targeting endothelial function may represent an attractive therapeutic option.

Endothelial Dysfunction in COVID-19: A Unifying Mechanism and a Potential Therapeutic Target.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) generated a worldwide emergency, until the declaration of the pandemic in March 2020. SARS-CoV-2 could be responsible for coronavirus disease 2019 (COVID-19), which goes from a flu-like illness to a potentially fatal condition that needs intensive care. Furthermore, the persistence of functional disability and long-term cardiovascular sequelae in COVID-19 survivors suggests that convalescent patients may suffer from post-acute COVID-19 syndrome, requiring long-term care and personalized rehabilitation. However, the pathophysiology of acute and post-acute manifestations of COVID-19 is still under study, as a better comprehension of these mechanisms would ensure more effective personalized therapies. To date, mounting evidence suggests a crucial endothelial contribution to the clinical manifestations of COVID-19, as endothelial cells appear to be a direct or indirect preferential target of the virus. Thus, the dysregulation of many of the homeostatic pathways of the endothelium has emerged as a hallmark of severity in COVID-19. The aim of this review is to summarize the pathophysiology of endothelial dysfunction in COVID-19, with a focus on personalized pharmacological and rehabilitation strategies targeting endothelial dysfunction as an attractive therapeutic option in this clinical setting.

Clinical assessment of endothelial function in convalescent COVID-19 patients: a meta-analysis with meta-regressions.

BACKGROUND: Endothelial dysfunction has been proposed to play a key role in the pathogenesis of coronavirus disease 2019 (COVID-19) and its post-acute sequelae. Flow-mediated dilation (FMD) is recognized as an accurate clinical method to assess endothelial function. Thus, we performed a meta-analysis of the studies evaluating FMD in convalescent COVID-19 patients and controls with no history of COVID-19. METHODS: A systematic literature search was conducted in the main scientific databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using the random effects method, differences between cases and controls were expressed as mean difference (MD) with 95% confidence intervals (95% CI). The protocol was registered on PROSPERO with reference number CRD42021289684. RESULTS: Twelve studies were included in the final analysis. A total of 644 convalescent COVID-19 patients showed significantly lower FMD values as compared to 662 controls (MD: -2.31%; 95% CI: -3.19, -1.44; p < 0.0001). Similar results were obtained in the sensitivity analysis of the studies that involved participants in either group with no cardiovascular risk factors or history of coronary artery disease (MD: -1.73%; 95% CI: -3.04, -0.41; p = 0.010). Interestingly, when considering studies separately based on enrolment within or after 3 months of symptom onset, results were further confirmed in both short- (MD: -2.20%; 95% CI: -3.35, -1.05; p < 0.0001) and long-term follow-up (MD: -2.53%; 95% CI: -4.19, -0.86; p = 0.003). Meta-regression models showed that an increasing prevalence of post-acute sequelae of COVID-19 was linked to a higher difference in FMD between cases and controls (Z-score: -2.09; p = 0.037). CONCLUSIONS: Impaired endothelial function can be documented in convalescent COVID-19 patients, especially when residual clinical manifestations persist. Targeting endothelial dysfunction through pharmacological and rehabilitation strategies may represent an attractive therapeutic option.Key messagesThe mechanisms underlying the post-acute sequelae of coronavirus disease 2019 (COVID-19) have not been fully elucidated.Impaired endothelial function can be documented in convalescent COVID-19 patients for up to 1 year after infection, especially when residual clinical manifestations persist.Targeting endothelial dysfunction may represent an attractive therapeutic option in the post-acute phase of COVID-19.

[Coronary computed tomography: current role and future perspectives for cardiovascular risk stratification]. / L'impiego della TC coronarica per la stratificazione del rischio cardiovascolare: evidenze e prospettive dopo lo studio CONFIRM.

Atherosclerotic coronary artery disease (CAD) is a major cause of morbidity and mortality. The majority of cardiovascular events, more than 50% of CAD deaths, occur in previously asymptomatic individuals at intermediate cardiovascular risk, highlighting the relevance of accurate individual risk assessment to decrease cardiovascular events through more appropriate targeting of preventive measures. In the last decades, the development of non-invasive imaging techniques have prompted interest in imaging of atherosclerosis. Coronary computed tomography provides the opportunity to assess the deposition of calcium in the coronary tree and to non-invasively image coronary vessels. Both information are useful for risk stratification of asymptomatic subjects or of subjects with suspected CAD.

[From myocardium to the atherosclerotic plaque: new perspectives in cardiologic imaging]. / Dal miocardio alla placca aterosclerotica: le nuove prospettive dell'imaging in cardiologia.

Molecular imaging is an innovative and promising approach in cardiology for functional characterization of atherosclerosis. Nuclear, ultrasound and magnetic resonance imaging have been used for assessment of atherosclerosis of large and small arteries in several clinical and experimental studies. Positron Emission Tomography with fluorodeoxyglucose can measure metabolic activity and vulnerability of atherosclerotic plaques, identifying individuals at risk of future cardiovascular events. Magnetic resonance imaging can quantify carotid artery inflammation using iron oxide nanoparticles as contrast agent. In addition, macrophage accumulation of iron particles in atherosclerotic plaques may allow monitoring of inflammation during drug therapy, whereas contrast-enhanced ultrasound imaging may detect plaque neovascularization. Currently, technical factors, including cardiac and diaphragmatic motion and small size of coronary vessels, limit routine application of these techniques for coronary imaging. Purpose of this review is to describe state of the art and potential areas of clinical applications of molecular imaging of atherosclerosis.

[Clinical and therapeutic value of carotid intima-media thickness]. / Il valore clinico e terapeutico dello Spessore Medio-Intimale Carotideo.

Carotid Intima Media Thickness (IMT) has been widely used to predict cardiovascular events in primary and secondary prevention studies. Yet, the power of IMT to reclassify risk level on top of conventional risk assessment based on classical risk factors remains unsettled. In fact, recent data indicate that the prognostic power of IMT is lower than that provided by the identification of carotid plaques. The role of IMT as surrogate endpoint to assess the efficacy of cardiovascular protective therapies is also still debated. In fact, no studies have ever been designed and powered to show a relationship between changes in carotid IMT during follow-up and cardiovascular events. Recently, two meta-analysis of trials using IMT as surrogate endpoint failed to demonstrate an association between IMT regression and cardiovascular events. The reasons for the lack of predictive role for changes in IMT are uncertain. It has been shown that IMT is not a pure atherosclerotic index, being substantially affected by age and hemodynamic factors including blood pressure and vessel wall shear stress. In addition, the status of carotid vessels does not strictly reflect that of coronary arteries. Finally, intra and inter-observer variability of measurements may further limit the association between IMT changes in individual patients and cardiovascular risk. Thus, IMT represents a valuable risk marker in population studies but its role for tailoring cardiovascular therapy in clinical practice remains currently uncertain.

[Metabolic and cardiovascular effects of combined antiretroviral therapy in patients with HIV infection. Systematic review of literature]. / Effetti metabolici e cardiovascolari della terapia antiretrovirale combinata in pazienti con infezione da HIV. Rassegna sistematica della letteratura.

In HIV infected patients an increased incidence of cardiac events has been reported since the introduction of highly active antiretroviral therapy (HAART). Antiretroviral drugs' regimens are, in fact, associated with several metabolic side effects, such as dyslipidemia, impaired glucose metabolism and abnormal body fat distribution, that increase cardiovascular risk of HIV subjects. In addition, HIV infection itself, the chronic inflammatory status and the frequent presence in this population of traditional risk factors contribute to an higher incidence of cardio and cerebrovascular events. In last years several studies showed the occurrence of carotid vascular impairment in patients treated with protease inhibitors (PI). Similarly the DAD Study reported an increase of 26% of the risk of myocardial infarction in patients on HAART and that this risk was independently associated with longer exposure to PI, after multivariate adjustments. A correct evaluation of the metabolic status before starting HAART and an adequate control of drugs-related metabolic abnormalities may reduce the incidence of cardiac events and still improve HIV patients prognosis. This review will focus on the metabolic effects of antiretroviral drugs and on the contribution of combination antiretroviral therapy on cardiovascular risk.

Clinical Assessment of Endothelial Function in Convalescent COVID-19 Patients Undergoing Multidisciplinary Pulmonary Rehabilitation.

BACKGROUND: Growing evidence points to a key role of endothelial dysfunction in the pathogenesis of COVID-19. In this study, we evaluated changes in endothelium-dependent flow-mediated dilation (FMD) in a cohort of convalescent COVID-19 patients undergoing pulmonary rehabilitation (PR). METHODS: After swab test negativization, convalescent COVID-19 patients referring to a post-acute care facility for PR were consecutively screened for inclusion. Study procedures were performed at the time of hospitalization and discharge. RESULTS: We enrolled 82 convalescent COVID-19 patients (85.4% males, mean age 60.4 years). After PR, a significant improvement in most pulmonary function tests and exercise capacity was documented. FMD changed from 2.48% ± 2.01 to 4.24% ± 2.81 (p < 0.001), corresponding to a 70.9% increase. Significantly higher changes in FMD were found in patients without a history of vascular events as compared to those with (+2.04% ± 2.30 vs. +0.61% ± 1.83, p = 0.013). Values of forced expiratory volume in 1 s (FEV1%), forced vital capacity (FVC%) and diffusion capacity for carbon monoxide (DLCO%) significantly and directly correlated with FMD both at baseline and after PR. Patients with normal FEV1% (≥80% predicted) during the overall study period or those normalizing FEV1% after PR showed a more significant FMD change as compared to patients with persistently impaired FEV1% (<80% predicted) (p for trend = 0.029). This finding was confirmed in a multivariate analysis. CONCLUSIONS: Clinically evaluated endothelial function improves after PR in convalescent COVID-19 patients. A direct and persistent association between the severity of pulmonary and vascular disease can be hypothesized. Endothelial function testing may be useful in the follow-up of convalescent COVID-19 patients.