AimsCarotid–femoral pulse wave velocity (PWV), a direct measure of aortic stiffness, has become increasingly important for total cardiovascular (CV) risk estimation. Its application as a routine tool for clinical patient evaluation has been hampered by the absence of reference values. The aim of the present study is to establish reference and normal values for PWV based on a large European population.Methods and resultsWe gathered data from 16 867 subjects and patients from 13 different centres across eight European countries, in which PWV and basic clinical parameters were measured. Of these, 11 092 individuals were free from overt CV disease, non-diabetic and untreated by either anti-hypertensive or lipid-lowering drugs and constituted the reference value population, of which the subset with optimal/normal blood pressures (BPs) (n = 1455) is the normal value population. Prior to data pooling, PWV values were converted to a common standard using established conversion formulae. Subjects were categorized by age decade and further subdivided according to BP categories. Pulse wave velocity increased with age and BP category; the increase with age being more pronounced for higher BP categories and the increase with BP being more important for older subjects. The distribution of PWV with age and BP category is described and reference values for PWV are established. Normal values are proposed based on the PWV values observed in the non-hypertensive subpopulation who had no additional CV risk factors.ConclusionThe present study is the first to establish reference and normal values for PWV, combining a sizeable European population after standardizing results for different methods of PWV measurement.

Abstract-Left ventricular (LV) mass and geometry predict risk for cardiovascular events in hypertension. Regression of LV hypertrophy (LVH) may imply an important prognostic significance. The relation between changes in LV geometry during antihypertensive treatment and subsequent prognosis has not yet been determined. A total of 436 prospectively identified uncomplicated hypertensive subjects with a baseline and follow-up echocardiogram (last examination 72Ϯ38 months apart) were followed for an additional 42Ϯ16 months. Their family doctor gave antihypertensive treatment. After the last follow-up echocardiogram, a first cardiovascular event occurred in 71 patients. Persistence of LVH from baseline to follow-up was confirmed as an independent predictor of cardiovascular events. Cardiovascular morbidity and mortality were significantly greater in patients with concentric (relative wall thickness Ն0.44) than in those with eccentric geometry (relative wall thickness Ͻ0.44) in patients presenting with LVH (Pϭ0.002) and in those without LVH (Pϭ0.002) at the follow-up echocardiogram. The incidence of cardiovascular events progressively increased from the first to the third tertile of LV mass index at follow-up (partition values 91 and 117 g/m 2 ), but for a similar value of LV mass index it was significantly greater in those with concentric geometry (OR: 4.07; 95% CI: 1.49 to 11.14; Pϭ0.004 in the second tertile; OR: 3.45; 95% CI: 1.62 to 7.32; Pϭ0.001 in the third tertile; PϽ0.0001 in concentric versus eccentric geometry). Persistence or development of concentric geometry during follow-up may have additional prognostic significance in hypertensive patients with and without LVH.

Background Patients with cancer are considered highly vulnerable to the recent coronavirus disease 2019 (COVID‐19) pandemic. However, there are still few data on COVID‐19 occurring in hematologic patients. Methods One hundred two patients with COVID‐19 symptoms and a nasopharyngeal swab positive for severe acute respiratory syndrome coronavirus 2 seen at 2 hematologic departments located in Lombardy, Italy, during March 2020 were studied. Risk factors for acquiring COVID‐19 were analyzed by comparisons of patients with COVID‐19 and the standard hematologic population managed at the same institutions in 2019. Thirty‐day survival was compared with the survival of matched uninfected control patients with similar hematologic disorders and nonhematologic patients affected by COVID‐19. Results Male sex was significantly more prevalent in patients with COVID‐19. The infection occurred across all different types of hematologic disease; however, the risk of acquiring a COVID‐19 infection was lower for patients with chronic myeloproliferative neoplasms, including chronic myeloid leukemia, and higher for patients with immune‐mediated anemia on immunosuppressive‐related treatments. The 30‐day mortality rate was 39.2%, which was higher than the rates for nonhematologic patients with COVID‐19 (23.5%; P = .02) and uninfected hematologic controls (3%; P < .001). The severity of the respiratory syndrome at presentation and active hematologic treatment were independently associated with a worse prognosis. Neither diagnosis nor disease status affected the prognosis. The worst prognosis was demonstrated among patients on active hematologic treatment and those with more severe respiratory syndrome at COVID‐19 presentation. Conclusions During the COVID‐19 pandemic, patients should be advised to seek medical attention at the earliest signs of dyspnea and/or respiratory infection. Physicians should perform a risk‐benefit analysis to determine the impact of temporarily deferring nonlifesaving treatments versus the risk of adverse outcomes associated with COVID‐19. Lay Summary Coronavirus disease 2019 (COVID‐19) infection occurs across all different types of hematologic disease; however, the risk of acquiring it is lower for patients with chronic myeloproliferative neoplasms, including chronic myeloid leukemia, and higher for patients with immune‐mediated anemia on immunosuppressive treatment. The 30‐day mortality rate is 39.2%, which is far higher than the rates for both uninfected hematologic controls (3%; P < .001) and nonhematologic patients with COVID‐19 (23.5%; P = .02) despite matching for age, sex, comorbidities, and severity of disease. Variables independently associated with a worse prognosis are the severity of the respiratory syndrome at presentation and any type of active hematologic treatment. Neither diagnosis nor disease status influence the prognosis.

Several studies have shown that aortic stiffness was an independent predictor for cardiovascular events. However, data are less consistent concerning carotid stiffness. We analyzed the determinants of the discrepancies between aortic and carotid stiffness in different populations with contrasting cardiovascular risk factors: 94 healthy normotensives (NT), 243 nondiabetic hypertensives (HT), and 126 patients with hypertension and type 2 diabetes (T2D). Aortic stiffness was measured with carotid-femoral pulse wave velocity. Common carotid stiffness was determined from the relative stroke change in diameter (measured with a high-resolution echotracking system) and carotid pulse pressure (measured with applanation tonometry) and was expressed in the same dimensions as pulse wave velocity (m/s). We identified the various factors explaining the discrepancies between aortic and carotid stiffness by multivariate analysis of the residuals of the correlation between aortic and carotid stiffness. The strength of the correlation between aortic and carotid stiffness became weaker as the number of cardiovascular risk factors increased (NT, r2=0.41; HT, r2=0.16; and T2D, r2=0.11), whereas we observed the opposite for the discrepancies (residuals) between aortic and carotid stiffness, of which an increasing part was explained (11% in NT, 22% in HT, and 45% in T2D) primarily by aging. In conclusion, although carotid-femoral pulse wave velocity and carotid stiffness provided similar information on the impact of aging on large artery stiffness in normal subjects, this was not the case for high blood pressure and/or diabetes. In these cases, the aorta stiffened more than the carotid artery with age and other cardiovascular risk factors.

Abstract-Assessment of appropriateness of left ventricular mass (LVM) for a given workload may better stratify hypertensive patients. Inappropriate LVM may reflect the interaction of genetic and neurohumoral factors other than blood pressure playing a significant role in myocardial growth. Primary aldosteronism (PA) represents a clinical model useful in assessing the effect of aldosterone increase on LVM. The aim of this study was to evaluate the inappropriateness of LVM in patients with PA. In 125 patients with PA (54 females; adrenal hyperplasia in 73 and adenoma in 52 patients) and in 125 age-, sex-, and blood pressure-matched, essential hypertensive patients, echocardiography was performed. The appropriateness of LVM was calculated by the ratio of observed LVM to the predicted value using a reference equation. In all of the subjects plasma renin activity and aldosterone, as well as clinic and 24-hour blood pressure, were measured. The prevalence of inappropriate LVM was greater in patients with traditionally defined left ventricular hypertrophy (70% and 44%, respectively; Pϭ0.02) but also in patients without left ventricular hypertrophy (17% and 9%, respectively; Pϭ0.085). In PA patients, a correlation was observed between the ratio of observed:predicted LVM and the ratio of aldosterone:plasma renin activity levels (rϭ0.29; Pϭ0.003) or the postinfusion aldosterone concentration (rϭ0.44; Pϭ0.004; nϭ42). In conclusion, in patients with PA, the prevalence of inappropriate LVM is increased, even in the absence of traditionally defined left ventricular hypertrophy. The increase in aldosterone levels could contribute to the increase of LV mass exceeding the amount needed to compensate hemodynamic load. (Hypertension. 2008;52:529-534.)

The presence of endothelial dysfunction, as evaluated by flow-mediated vasodilatation of the brachial artery, identifies hypertensive patients at increased risk of nonfatal and fatal cardiovascular events.

Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

In recent years, serum uric acid (SUA) as a determinant of cardiovascular (CV) risk has gained interest. Epidemiological, experimental and clinical data show that patients with hyperuricaemia SUA are at increased risk of cardiac, renal and vascular damage and CV events. There is now some evidence to suggest that urate-lowering treatment may reduce CV risk in this group and, thus, may represent a new strategy in risk reduction.