Vascular Dysfunction of COVID-19 Is Partially Reverted in the Long-Term.

BACKGROUND: COVID-19 is characterized by severe inflammation during the acute phase and increased aortic stiffness in the early postacute phase. In other models, aortic stiffness is improved after the reduction of inflammation. We aimed to evaluate the mid- and long-term effects of COVID-19 on vascular and cardiac autonomic function. The primary outcome was aortic pulse wave velocity (aPWV). METHODS: The cross-sectional Study-1 included 90 individuals with a history of COVID-19 and 180 matched controls. The longitudinal Study-2 included 41 patients with COVID-19 randomly selected from Study-1 who were followed-up for 27 weeks. RESULTS: Study-1: Compared with controls, patients with COVID-19 had higher aPWV and brachial PWV 12 to 24 (but not 25-48) weeks after COVID-19 onset, and they had higher carotid Young's elastic modulus and lower distensibility 12 to 48 weeks after COVID-19 onset. In partial least squares structural equation modeling, the higher the hs-CRP (high-sensitivity C-reactive protein) at hospitalization was, the higher the aPWV 12 to 48 weeks from COVID-19 onset (path coefficient: 0.184; P=0.04). Moreover, aPWV (path coefficient: -0.186; P=0.003) decreased with time. Study-2: mean blood pressure and carotid intima-media thickness were comparable at the end of follow-up, whereas aPWV (-9%; P=0.01), incremental Young's elastic modulus (-17%; P=0.03), baroreflex sensitivity (+28%; P=0.049), heart rate variability triangular index (+15%; P=0.01), and subendocardial viability ratio (+12%; P=0.01×10-4) were significantly improved. There was a trend toward improvement in brachial PWV (-6%; P=0.14) and carotid distensibility (+18%; P=0.05). Finally, at the end of follow-up (48 weeks after the onset of COVID-19) aPWV (+6%; P=0.04) remained significantly higher in patients with COVID-19 than in control subjects. CONCLUSIONS: COVID-19-related arterial stiffening involves several arterial tree portions and is partially resolved in the long-term.

Biomarkers Predict In-Hospital Major Adverse Cardiac Events in COVID-19 Patients: A Multicenter International Study.

BACKGROUND: The COVID-19 pandemic carries a high burden of morbidity and mortality worldwide. We aimed to identify possible predictors of in-hospital major cardiovascular (CV) events in COVID-19. METHODS: We retrospectively included patients hospitalized for COVID-19 from 10 centers. Clinical, biochemical, electrocardiographic, and imaging data at admission and medications were collected. Primary endpoint was a composite of in-hospital CV death, acute heart failure (AHF), acute myocarditis, arrhythmias, acute coronary syndromes (ACS), cardiocirculatory arrest, and pulmonary embolism (PE). RESULTS: Of the 748 patients included, 141(19%) reached the set endpoint: 49 (7%) CV death, 15 (2%) acute myocarditis, 32 (4%) sustained-supraventricular or ventricular arrhythmias, 14 (2%) cardiocirculatory arrest, 8 (1%) ACS, 41 (5%) AHF, and 39 (5%) PE. Patients with CV events had higher age, body temperature, creatinine, high-sensitivity troponin, white blood cells, and platelet counts at admission and were more likely to have systemic hypertension, renal failure (creatinine ≥ 1.25 mg/dL), chronic obstructive pulmonary disease, atrial fibrillation, and cardiomyopathy. On univariate and multivariate analysis, troponin and renal failure were associated with the composite endpoint. Kaplan-Meier analysis showed a clear divergence of in-hospital composite event-free survival stratified according to median troponin value and the presence of renal failure (Log rank p < 0.001). CONCLUSIONS: Our findings, derived from a multicenter data collection study, suggest the routine use of biomarkers, such as cardiac troponin and serum creatinine, for in-hospital prediction of CV events in patients with COVID-19.

Resistive index of ophthalmic artery as an imaging biomarker of hypertension-related vascular and kidney damage.

Aim: Resistive index of ophthalmic artery (RI-OA) is associated with atherosclerotic diseases. The aim of this study was to evaluate the association of RI-OA and hypertension-related vascular and kidney damage. Materials and methods: Two-hundred and eighty hypertensive patients underwent evaluation of RI-OA, carotid atherosclerosis and level of 24 h albuminuria. Results: Albuminuria and carotid atherosclerosis were positively associated with RI-OA independently of other cardiovascular risk factors. Receiver-operating characteristic curve analysis allowed us to calculate a cut-off value of RI-OA >0.625, which would be suspicious about the existence of atherosclerotic disease. Conclusion: The ophthalmic vascular circulation allows to study connections between macro- and microcirculation in vivo. RI-OA could be a useful marker for a better stratification of the risk of developing kidney and cardiovascular disease.

Relationship of choroidal thickness with pulsatile hemodynamics in essential hypertensive patients.

Controversy exists about the association of choroidal thickness (CTh) with blood pressure (BP) values. There is some evidence suggesting that central hemodynamics changes are associated with microvascular disease. Our study was aimed to assess the relationships between CTh and clinic and 24-h BP and between CTh and estimated 24-h aortic pulse pressure (aPP), 24-h aortic systolic BP (aSBP), and 24-h aortic augmentation index (aAIx) in a group of hypertensive patients. We enrolled 158 hypertensive subjects (mean age 48 ± 13 years) all of which underwent evaluation of the choroidal district by Swept-Source optical coherence tomography (SS-OCT) and 24-h BP monitoring, in order to measure peripheral BP and to estimate central hemodynamic parameters. Inverse significant correlations of clinic PP, 24-h aPP, 24-h aSBP, and 24-h aAIx with thicknesses of central ring, inner ring, and outer ring of the choroid and its overall average were found. The strongest of these correlations was that relating 24-h aPP with overall average choroidal thickness (r = -.531; P < .001). When we divided the study population in subjects with 24-h aPP above and below the median value (35 mm Hg), CTh were thinner in subjects with higher values of 24-aPP as compared to those with lower ones, even after adjustment for age, and other potential confounders. The relationships of CTh with 24-h aPP remained significant also taking into account the effects of various covariates in linear multiple regression analyses. Our findings support the concept of a cross-talk between macro- and microcirculation.

Left ventricular hypertrophy in chronic kidney disease: A diagnostic criteria comparison.

BACKGROUND AND AIMS: CKD patients have a high prevalence of LVH and this leads to an increase of cardiovascular risk. The aim of this study was to assess the prevalence of left ventricular hypertrophy (LVH) and left ventricular geometry in a group of 293 hypertensive patients with stage 2-5 chronic kidney disease (CKD), compared with 289 essential hypertensive patients with normal renal function. METHODS AND RESULTS: All patients underwent echocardiographic examination. Patients on stage 1 CKD, dialysis treatment, or with cardiovascular diseases were excluded. LVH was observed in 62.8% of patients with CKD and in 51.9% of essential hypertensive patients (P < 0.0001). We found increasingly higher left ventricular diameters, thicknesses, and mass from stage 2-5 CKD. Distribution of concentric and eccentric LVH was not very different between the two groups. However, after introducing mixed hypertrophy, the difference between the two groups group was disclosed (P = 0.027). Multiple regression analysis confirmed that the association between renal function and left ventricular mass (ß -0.287; P < 0.0001) was independent by potential confounders. Diastolic function was significantly worse in patients with CKD, especially in more advanced stages. CONCLUSION: Our study confirms that LVH is highly prevalent in patients with CKD, especially by using the most recent cut off; in this population, LVH is often characterized by the simultaneous increase of wall thicknesses and diameters with negative effects on diastolic function.

Inflammatory activation and endothelial dysfunction markers in patients with permanent atrial fibrillation: a cross-sectional study.

In recent years a growing body of evidence supported the role of inflammation in the initiation, maintenance and outcome of atrial fibrillation (AF). Nevertheless, despite a large amount of information, whether AF or the underlying structural heart disease (SHD) is the cause of the inflammatory process is still under debate. We, therefore, sought to determine if the inflammatory process reflect an underlying disease or the arrhythmia 'per se'. We evaluated plasma levels of soluble Interleukin 2 Receptor Alpha (sIL-2Rα), TNF-α and IL-18 in 100 consecutive patients with permanent AF, (43 with a SHD and 57 without a SHD) compared to 121 age and sex-matched controls which had normal sinus rhythm. We also evaluated the endothelial function in both groups of patients using reactive hyperemia index (RHI) values measured by Endo-PAT2000. Compared to controls, AF patients showed higher circulating levels of inflammatory markers and a lower mean value of RHI. At multiple logistic regression analysis, the inflammatory markers and RHI were significantly associated with AF presence, whereas ROC curve analysis had good sensitivity and specificity in inflammatory variables and RHI for AF presence. No significant association was observed in the group of permanent AF patients, between inflammatory markers and the presence of an underlying SHD. These findings could help to clarify the role of inflammation in subjects with AF and suggest that the markers of systemic inflammation are not associated with the underlying cardiovascular disease, rather with the atrial fibrillation 'per se'.

Choroidal thickness is associated with renal hemodynamics in essential hypertension.

The choroid is the most vascularized structure of the eye and plays a central role in the development of the retinal vascular changes that occur in arterial hypertension. Changes of choroidal thickness (ChT) assessed by optical coherence tomography (OCT) technology could reflect the vascular complications of hypertension. Also, intrarenal hemodynamic damage, associated with endothelial dysfunction, demonstrated to be a good indicator of systemic morphofunctional arterial impairment. The aim of this study is to assess the relationship between ChT and renal hemodynamics in subjects with essential hypertension. Routine laboratory tests, clinical history, and physical examination, including blood pressure assessment, were performed in 90 subjects with essential hypertension. All patients underwent Doppler ultrasonographic evaluation of intra-renal hemodynamics and OCT imaging to assess ChT. When subjects were divided in two groups based on renal resistive index (RRI), group I (RRI ≥ 75% percentile) showed significantly lower values of ChT than group II (RRI < 75% percentile) (P < .001). When divided in two groups based on the ChT median values, patients with lower ChT had significantly higher RRI values than those with ChT above the median values (P < .05). In multivariate model including age, eGFR, and other variables as confounding factors, RRI ≥ 75% was independently associated with ChT. ChT was significantly correlated with renal resistive index in subjects with essential hypertension, confirmed in multivariate analyses. This result could be referred to changes in vascular elastic properties that occur in retinal and intrarenal vascular system probably due to oxidative stress and endothelial dysfunction commonly found in early complications of hypertension.

Evaluation of Unattended Automated Office, Conventional Office and Ambulatory Blood Pressure Measurements and Their Correlation with Target Organ Damage in an Outpatient Population of Hypertensives: Study Design and Methodological Aspects.

Accurate measurement of blood pressure (BP) has a pivotal role in the management of patients with arterial hypertension. Recently, introduction of unattended office BP measurement has been proposed as a method allowing more accurate management of hypertensive patients and prediction of hypertension-mediated target organ damage (HMOD). This approach to BP measurement has been in particular proposed to avoid the white coat effect (WCE), which can be easily assessed once both attended and unattended BP measurements are obtained. In spite of its interest, the role of WCE in predicting HMOD remains largely unexplored. To fill this gap the Young Investigator Group of the Italian Hypertension Society (SIIA) conceived the study "Evaluation of unattended automated office, conventional office and ambulatory blood pressure measurements and their correlation with target organ damage in an outpatient population of hypertensives". This is a no-profit multicenter observational study aiming to correlate attended and unattended BP measurements for quantification of WCE and to correlate WCE with markers of HMOD, such us left ventricular hypertrophy, left atrial dilatation, and peripheral atherosclerosis. The Ethical committee of the Federico II University hospital has approved the study.

Relationship of a Body Shape Index and Body Roundness Index with carotid atherosclerosis in arterial hypertension.

BACKGROUND AND AIMS: A Body Shape Index (ABSI) and Body Roundness Index (BRI) are two new anthropometric adiposity indices that have shown to be associated better than BMI with adipose abdominal tissue, with the onset of diabetes and the risk of premature death. Little is known about the influence of ABSI and BRI on subclinical vascular damage. The study was aimed to assess the relationship between ABSI and BRI with carotid atherosclerosis damage in subjects with arterial hypertension. METHODS AND RESULTS: A total of 468 patients with arterial hypertension (30-80 years old) were enrolled; adiposity indices were calculated (BMI, WC, ABSI, BRI) and carotid ultrasonographic examination was performed to detect atherosclerotic damage (IMT or atherosclerotic plaque). BRI, but not ABSI, was higher in subjects with IMT> 0.90 mm in comparison to those with a lower IMT (p < 0.001), whereas patients with carotid plaques showed higher values of ABSI (p = 0.001), as well as of BRI (p = 0.003). Linear regression analysis disclosed significant correlation of IMT with ABSI, BRI and BMI (all p < 0.001). In the multivariate analysis, BRI was independently correlated with cIMT (p = 0.015). On the contrary, ABSI did not show any independent association with cIMT. However, ABSI was strongly associated with carotid plaques in multiple logistic regression analysis after adjustment for potential confounding factors. When BRI or BMI replaced ABSI into the multivariate models, they did not show any independent correlation with carotid plaques. CONCLUSIONS: ABSI may be proposed as a better correlate of carotid atherosclerosis than the traditional measures of adiposity.

Is echocardiography mandatory for patients with chronic kidney disease?

This study aims at evaluating the prevalence of left ventricular diastolic dysfunction in a group of 319 hypertensive patients with stage 3b-4-5 chronic kidney disease (according to Kidney Disease Improving Global Outcomes classification), compared with 216 patients with essential hypertension and normal renal function. All patients underwent echocardiographic examination. Patients on stage 1-2-3a chronic kidney disease, dialysis treatment, or with previous manifestations of heart failure or other cardiovascular diseases were excluded. Patients with renal disease had significantly worse diastolic function (both considering trans-mitral flow and tissue Doppler imaging parameters). Diastolic dysfunction is found in 70.5% of the CKD group and in 41.6% of hypertensive patients (p < 0.0001). Multiple regression analysis shows an association between renal function and diastolic function (ß 0.223; p < 0.0001), independent of potential confounders. Our study shows that diastolic dysfunction is highly prevalent in patients with advanced chronic kidney disease; we posit that in this population, the risk of diastolic heart failure is very high. We think that patients with a marked decrease of glomerular filtration rate (GFR) must be considered at high risk for diastolic heart failure and should have an echocardiographic examination performed, even if asymptomatic and in the absence of evident cardiovascular disease.

Renal haemodynamics and coronary atherosclerotic burden are associated in patients with hypertension and mild coronary artery disease.

Intrarenal hemodynamic alterations are independent predictors of cardiovascular events in different populations. It has been hypothesized that there is an association between renal hemodynamics and coronary atherosclerotic burden in patients with hypertension. Therefore, the present study examined the associations between renal hemodynamics, coronary atherosclerotic burden and carotid atherosclerotic disease. A total of 130 patients with hypertension aged between 30-80 years who had been referred for an elective coronary angiography were enrolled in the present study. A duplex ultrasound of the intrarenal vasculature was performed to evaluate the resistive index (RI), pulsatility index (PI) and acceleration time (AT). The carotid intima-media thickness was additionally assessed. A coronary angiography was performed to detect the atherosclerotic burden using the Gensini Score (GS). Based on the GS values, subjects were divided into quintiles (I: ≤9; II: 9-17; III: 17-30; IV: 30-44; and V: GS >44) as well as in subjects with mild (GS ≤30) or severe coronary disease (GS >30). A weak significant difference in PI was identified among quintiles (P=0.041), whereas, RI and AT did not differ significantly. PI was associated with GS in the group with low coronary atherosclerotic burden (GS ≤30; P=0.047), whereas, no association was detected in subjects with GS >30. This association remained following adjustment for age and left ventricular ejection fraction (P=0.025). In conclusion, renal vascular alterations were associated with coronary atherosclerotic burden in patients with hypertension with mild coronary disease.

Inflammation and Aortic Pulse Wave Velocity: A Multicenter Longitudinal Study in Patients With Inflammatory Bowel Disease.

Background Inflammatory bowel disease ( IBD ) is characterized by a low prevalence of traditional risk factors, an increased aortic pulse-wave velocity ( aPWV ), and an excess of cardiovascular events. We have previously hypothesized that the cardiovascular risk excess reported in these patients could be explained by chronic inflammation. Here, we tested the hypothesis that chronic inflammation is responsible for the increased aPWV previously reported in IBD patients and that anti-TNFa (anti-tumor necrosis factor-alpha) therapy reduce aPWV in these patients. Methods and Results This was a multicenter longitudinal study. We enrolled 334 patients: 82 patients with ulcerative colitis, 85 patients with Crohn disease, and 167 healthy control subjects matched for age, sex, and mean blood pressure, from 3 centers in Europe, and followed them for 4 years (range, 2.5-5.7 years). At baseline, IBD patients had higher aPWV than controls. IBD patients in remission and those treated with anti-TNFa during follow-up experienced an aortic destiffening, whereas aPWV increased in those with active disease and those treated with salicylates ( P=0.01). Disease duration ( P=0.02) was associated with aortic stiffening as was, in patients with ulcerative colitis, high-sensitivity C-reactive protein during follow-up ( P=0.02). All these results were confirmed after adjustment for major confounders. Finally, the duration of anti-TNFa therapy was not associated with the magnitude of the reduction in aPWV at the end of follow-up ( P=0.85). Conclusions Long-term anti-TNFa therapy reduces aPWV , an established surrogate measure of cardiovascular risk, in patients with IBD . This suggests that effective control of inflammation may reduce cardiovascular risk in these patients.

Para-perirenal distribution of body fat is associated with reduced glomerular filtration rate regardless of other indices of adiposity in hypertensive patients.

Obesity is a well-known risk factor for the development and progression of chronic kidney disease. Recently, para-perirenal ultrasonographic fat thickness (PUFT) has shown to correlate with both total and visceral fat better than body mass index (BMI), waist circumference (WC), and other indices of obesity. Moreover, a local paracrine and mechanical action of the PUFT on kidney has been described in recent studies. Aim of our study was to assess the relationship between glomerular filtration rate (GFR) and PUFT in comparison with other anthropometric and ultrasonographic indices of adiposity. Two hundred and ninety-six hypertensive patients were enrolled. PUFT, cutis-rectis thickness and rectis-aorta thickness were obtained by ultrasonography. Anthropometric measures of adiposity were also measured. Estimated GFR was calculated using the CKD-EPI equation. Higher PUFT values were observed in patients with impaired renal function (P < 0.001), whereas no differences in BMI and WC were shown between groups divided by GFR. PUFT significantly correlated with GFR in all patients (r = -0.284; P < 0.001), with no differences in groups divided by sex, diabetes, or BMI. This association held in multivariate analyses also after correction for confounding factors, including other adiposity indices (P < 0.001). When receiver operating characteristic curves were built to detect a eGFR < 60 mL/minutes per 1.73 m2 , a PUFT value ≤3.725 cm showed a negative predictive value of 94.0%, with the largest area under the curve (AUC: 0.700) among the variables considered. In conclusion, the relationship between PUFT and GFR seems to be more accurate and less influenced by the bias affecting traditional indices of adiposity.