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Abstract Background Insulin resistance (IR) and serum uric acid (SUA) are closely interconnected: SUA contributes to adversely affects the insulin signaling pathway and contributes to IR, while IR is a known predictor for the development of hyperuricemia. The triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio has been proposed as an easily obtainable marker for IR. This research aimed to investigate the interaction between IR and glomerular filtration rate (GFR)-adjusted uricemia (SUA/GFR ratio) in determining CV risk in a large population cohort study. Methods Data from 18,694 subjects were analyzed from Uric acid Right foR heArt Healt (URRAH) database. The study evaluated the association between TG/HDL-C ratio and SUA/GFR ratio, as well as their impact on the development of outcomes during the follow-up study period. The primary endpoint was CV mortality. Results After a mean follow-up of 124 ± 64 months, 2,665 (14.2%) CV deaths occurred. The incidence of fatal and non-fatal CV events increased in parallel with the increase of TG/HDL-C quintiles. TG/HDL-C ratio showed a positive association with increasing of SUA/GFR ratio, even in non-diabetic patients. Multivariate analysis showed that the TG/HDL-C ratio increases the mortality risk even after adjustment for potential confounding factors. Finally, IR and GFR-adjusted hyperuricemia showed an additive effect on CV mortality. Conclusions Both IR and SUA/GFR ratio independently predict CV mortality, regardless of age, gender, BMI, diabetes, hypertension and statin use. The joint effect of the TG/HDL-C ratio and the elevated SUA/GFR ratio was greater than the presence of each single risk factor on CV mortality. This highlights the importance of monitoring these markers to better assess cardiovascular risk.

Background: Atrial fibrillation (AFIB), the most frequent cardiac arrhythmia, is a major risk factor for stroke, heart failure, and death. Because of the recent advances in AFIB management and the availability of new oral anticoagulants (OACs), there is a need for a systematic and predefined collection of contemporary data regarding its management and treatment. Methods: The objective of the ongoing ITALY-AFIB registry is to evaluate the long-term morbidity and mortality in patients with AFIB and to verify the implementation of the current guidelines for stroke prevention in these patients. The registry includes consecutive in- and out-patients with first diagnosed, paroxysmal, persistent, or permanent AFIB. In patients in sinus rhythm at entry, the qualifying episode of AFIB, confirmed by ECG diagnosis, had to have occurred within 1 year before entry. The clinical record form is web-based and accessible by personal keyword. Results: Enrolment into the registry started in the year 2013. In a current cohort of 2470 patients (mean age 75 ± 11 years, males 56%), the mean CHA2DS2-VASc score was 3.7 ± 1.8, and the mean HAS-BLED was 1.6 ± 0.9. There were no significant sex differences in the AFIB subtypes. At the end of the inclusion visit and after receiving knowledge of the web-based electronic estimate of risk for stroke and bleeding, the proportion of patients discharged with OACs was 80%. After exclusion of patients with first diagnosed AFIB (n = 397), the proportion of patients with prescription of OACs rose from 66% before the visit to 82% on discharge (p < 0.0001). Prescription of aspirin or other antiplatelet drugs fell from 18% before the visit to 10% on discharge (p < 0.0001). Conclusions: A web-based management of AFIB with automated estimation of risk profiles appears to favorably affect adherence to AFIB guidelines, based on a high proportion of patients treated with OACs and a substantial decline in the use of antiplatelet drugs.

Background Despite longstanding epidemiologic data on the association between increased serum triglycerides and cardiovascular events, the exact level at which risk begins to rise is unclear. The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension has conceived a protocol aimed at searching for the prognostic cutoff value of triglycerides in predicting cardiovascular events in a large regional‐based Italian cohort. Methods and Results Among 14 189 subjects aged 18 to 95 years followed‐up for 11.2 (5.3–13.2) years, the prognostic cutoff value of triglycerides, able to discriminate combined cardiovascular events, was identified by means of receiver operating characteristic curve. The conventional (150 mg/dL) and the prognostic cutoff values of triglycerides were used as independent predictors in separate multivariable Cox regression models adjusted for age, sex, body mass index, total and high‐density lipoprotein cholesterol, serum uric acid, arterial hypertension, diabetes, chronic renal disease, smoking habit, and use of antihypertensive and lipid‐lowering drugs. During 139 375 person‐years of follow‐up, 1601 participants experienced cardiovascular events. Receiver operating characteristic curve showed that 89 mg/dL (95% CI, 75.8–103.3, sensitivity 76.6, specificity 34.1, P

Abstract Introduction Vaccination strongly reduces the risk of hospitalization and death due to coronavirus disease 2019 (COVID-19). However, the severity of the acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and the degree of protection exerted over time by vaccination remains to be fully elucidated among hospitalized comorbid and vulnerable patients with SARS-CoV-2 infection. Methods We report a case series of nine hospitalized vulnerable patients who developed a SARS-CoV-2 infection during a cardiac rehabilitation inpatient program. Results Age ranged from 50 to 81 years. All but one patient had received at least three doses of anti-COVID-19 vaccine more than 4 months before the cardiac event. Indications for cardiac rehabilitation included acute coronary syndromes, congestive heart failure, heart valve surgery, and coronary artery bypass graft. After the confirmed diagnosis of SARS-CoV-2 infection, all patients developed symptoms. Eight patients developed at least one SARS-CoV-2-related complication, including a significant increase in high-sensitivity troponin I levels, new-onset hypoxemia, persistent atrial fibrillation, non-sustained ventricular tachycardia and recurrent sinus arrest, pericardial effusion, and a persistent increase in blood pressure. Conclusion Almost all patients developed complications which, however, did not evolve towards more severe expressions of the disease. These data suggest that even in this new phase of the pandemic, vaccination may exert a potential role to reduce the risk of progression towards more severe disease of SARS-CoV-2 infection in vulnerable patients with cardiovascular comorbidities.

High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular-risk phenotypes, including subclinical atherosclerosis. An interaction between plaques xanthine oxidase (XO) expression, SUA, and HDL-C has been recently postulated. Subjects from the URic acid Right for heArt Health (URRAH) study with carotid ultrasound and without previous cardiovascular diseases (CVD) (n = 6209), followed over 20 years, were included in the analysis. Hypertriglyceridemia (hTG) was defined as TG ≥ 150 mg/dL. Higher levels of SUA (hSUA) were defined as ≥5.6 mg/dL in men and 5.1 mg/dL in women. A carotid plaque was identified in 1742 subjects (28%). SUA and TG predicted carotid plaque (HR 1.09 [1.04–1.27], p < 0.001 and HR 1.25 [1.09–1.45], p < 0.001) in the whole population, independently of age, sex, diabetes, systolic blood pressure, HDL and LDL cholesterol and treatment. Four different groups were identified (normal SUA and TG, hSUA and normal TG, normal SUA and hTG, hSUA and hTG). The prevalence of plaque was progressively greater in subjects with normal SUA and TG (23%), hSUA and normal TG (31%), normal SUA and hTG (34%), and hSUA and hTG (38%) (Chi-square, 0.0001). Logistic regression analysis showed that hSUA and normal TG [HR 1.159 (1.002 to 1.341); p = 0.001], normal SUA and hTG [HR 1.305 (1.057 to 1.611); p = 0.001], and the combination of hUA and hTG [HR 1.539 (1.274 to 1.859); p = 0.001] were associated with a higher risk of plaque. Our findings demonstrate that SUA is independently associated with the presence of carotid plaque and suggest that the combination of hyperuricemia and hypertriglyceridemia is a stronger determinant of carotid plaque than hSUA or hTG taken as single risk factors. The association between SUA and CVD events may be explained in part by a direct association of UA with carotid plaques.

The objective of this study was to investigate the longitudinal association of metabolically healthy overweight/obese adults with major adverse cardiovascular events (MACE) and the effect of LDL-cholesterol levels on this association. This study was conducted with 15,904 participants from the URRAH study grouped according to BMI and metabolic status. Healthy metabolic status was identified with and without including LDL-cholesterol. The risk of MACE during 11.8 years of follow-up was evaluated with multivariable Cox regressions. Among the participants aged p = 0.012). However, when LDL-cholesterol < 130 mg/dL was included in the definition of healthy metabolic status, no increase in risk was found in the overweight/obese adults compared to the normal weight individuals (hazard ratio 0.70 (0.07–6.71, p = 0.75). The present data show that the risk of MACE is increased in metabolically healthy overweight/obese individuals identified according to standard criteria. However, when LDL-cholesterol is included in the definition, metabolically healthy individuals who are overweight/obese have no increase in risk.

Arterial hypertension is the most frequent cardiovascular risk factor all over the world, and it is one of the leading drivers of the risk of cardiovascular events and death. It is a complex trait influenced by heritable and environmental factors. To date, the World Health Organization estimates that 1.28 billion adults aged 30–79 years worldwide have arterial hypertension (defined by European guidelines as office systolic blood pressure ≥ 140 mmHg or office diastolic blood pressure ≥ 90 mmHg), and 7.1 million die from this disease. The molecular genetic basis of primary arterial hypertension is the subject of intense research and has recently yielded remarkable progress. In this review, we will discuss the genetics of arterial hypertension. Recent studies have identified over 900 independent loci associated with blood pressure regulation across the genome. Comprehending these mechanisms not only could shed light on the pathogenesis of the disease but also hold the potential for assessing the risk of developing arterial hypertension in the future. In addition, these findings may pave the way for novel drug development and personalized therapeutic strategies.

Several studies have detected a direct association between serum uric acid (SUA) and cardiovascular (CV) risk. In consideration that SUA largely depends on kidney function, some studies explored the role of the serum creatinine (sCr)-normalized SUA (SUA/sCr) ratio in different settings. Previously, the URRAH (URic acid Right for heArt Health) Study has identified a cut-off value of this index to predict CV mortality at 5.35 Units. Therefore, given that no SUA/sCr ratio threshold for CV risk has been identified for patients with diabetes, we aimed to assess the relationship between this index and CV mortality and to validate this threshold in the URRAH subpopulation with diabetes; the URRAH participants with diabetes were studied (n = 2230). The risk of CV mortality was evaluated by the Kaplan–Meier estimator and Cox multivariate analysis. During a median follow-up of 9.2 years, 380 CV deaths occurred. A non-linear inverse association between baseline SUA/sCr ratio and risk of CV mortality was detected. In the whole sample, SUA/sCr ratio > 5.35 Units was not a significant predictor of CV mortality in diabetic patients. However, after stratification by kidney function, values > 5.35 Units were associated with a significantly higher mortality rate only in normal kidney function, while, in participants with overt kidney dysfunction, values of SUA/sCr ratio > 7.50 Units were associated with higher CV mortality. The SUA/sCr ratio threshold, previously proposed by the URRAH Study Group, is predictive of an increased risk of CV mortality in people with diabetes and preserved kidney function. While, in consideration of the strong association among kidney function, SUA, and CV mortality, a different cut-point was detected for diabetics with impaired kidney function. These data highlight the different predictive roles of SUA (and its interaction with kidney function) in CV risk, pointing out the difference in metabolic- and kidney-dependent SUA levels also in diabetic individuals.

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007.

AbstractBackground Hypertension is characterised by a high prevalence, low awareness and poor control among rheumatoid arthritis (RA) patients. Correct blood pressure (BP) measurement is highly important in these subjects. The “unattended” BP measurement aims to reduce the “white-coat effect,” a phenomenon associated with cardiovascular risk. Data on “unattended” BP measurement in RA and its impact on hypertensive organ damage are very limited.Methods BP was measured in the same patient both traditionally (“attended” BP) and by the “unattended” protocol (3 automated office BP measurements, at 1-min intervals, after 5 min of rest, with patient left alone) by a randomised cross-over design. Patients underwent clinical examination, 12-lead electrocardiography and trans-thoracic echocardiography to evaluate cardiac damage.Results Sixty-two RA patients (mean age 67 ± 9 years, 87% women) were enrolled. Hypertension was diagnosed in 79% and 66% of patients according to ACC/AHA and ESC/ESH criteria, respectively. Concordance correlation coefficients between the two techniques were 0.55 (95%, CI 0.38–0.68) for systolic BP and 0.73 (95%, CI 0.60–0.82) for diastolic BP. “Unattended” (121.7/68.6 mmHg) was lower than “attended” BP (130.5/72.8 mmHg) for systolic and diastolic BP (both p

Abstract Background Several studies addressed the association between fragmented QRS (fQRS) on 12-lead EKG and left ventricular (LV) dysfunction in patients with a variety of cardiovascular disorders. We tested such association in healthy individuals. Methods Out of 500 healthy participants without -overt cardiovascular disease from the Shiraz Heart Study cohort, we identified 20 subjects with fQRS (cases) and 20 peers without fQRS (controls). Global LV longitudinal strain (GLS) was measured by speckle tracking echocardiography in the two groups. Comparison was made between case and control groups by using chi-square or independent sample t-test or ANOVA. Results Age, gender, ejection fraction, LV volume and dimensions did not differ between the case and the control groups. Overall, 14 subjects out of 40 had reduced GLS (≤20%) and 10 of them (25%) had fQRS. GLS was significantly lower in the group with fQRS than in the control group (19.9 ± 1.8 vs 21.4 ± 1.6; p = 0.009). Conclusions Healthy subjects with fQRS present regional LV systolic dysfunction, assessed by GLS, in the presence of a normal ejection fraction. These data suggest that fQRS may be a promising tool to identify apparently healthy subjects with regional LV systolic dysfunction.

Several outcome-based prospective investigations have provided solid data which support the prognostic value of 24 h ambulatory blood pressure over and beyond cardiovascular traditional risk factors. Average 24 h, daytime, and nighttime blood pressures are the principal components of the ambulatory blood pressure profile that have improved cardiovascular risk stratification beyond traditional risk factors. Furthermore, several additional ambulatory blood pressure measures have been investigated. The correct interpretation in clinical practice of ambulatory blood pressure monitoring needs a standardization of methods. Several algorithms for its clinical use have been proposed. Implementation of the results of ambulatory blood pressure monitoring in the management of individual subjects with the aim of improving risk stratification is challenging. We suggest that clinicians should focus attention on ambulatory blood pressure components which have been proven to act as the main independent predictors of outcome (average 24 h, daytime, and nighttime blood pressure, pulse pressure, dipping status, BP variability).

High serum uric acid (SUA) and triglyceride (TG) levels might promote high-cardiovascular risk phenotypes across the cardiometabolic spectrum. However, SUA predictive power in the presence of normal and high TG levels has never been investigated. We included 8124 patients from the URic acid Right for heArt Health (URRAH) study cohort who were followed for over 20 years and had no established cardiovascular disease or uncontrolled metabolic disease. All-cause mortality (ACM) and cardiovascular mortality (CVM) were explored by the Kaplan–Meier estimator and Cox multivariable regression, adopting recently defined SUA cut-offs for ACM (≥4.7 mg/dL) and CVM (≥5.6 mg/dL). Exploratory analysis across cardiometabolic subgroups and a sensitivity analysis using SUA/serum creatinine were performed as validation. SUA predicted ACM (HR 1.25 [1.12–1.40], p < 0.001) and CVM (1.31 [1.11–1.74], p < 0.001) in the whole study population, and according to TG strata: ACM in normotriglyceridemia (HR 1.26 [1.12–1.43], p < 0.001) and hypertriglyceridemia (1.31 [1.02–1.68], p = 0.033), and CVM in normotriglyceridemia (HR 1.46 [1.23–1.73], p < 0.001) and hypertriglyceridemia (HR 1.31 [0.99–1.64], p = 0.060). Exploratory and sensitivity analyses confirmed our findings, suggesting a substantial role of SUA in normotriglyceridemia and hypertriglyceridemia. In conclusion, we report that SUA can predict ACM and CVM in cardiometabolic patients without established cardiovascular disease, independent of TG levels.

Hypertension is the most frequent cardiovascular risk factor all over the world. It remains a leading contributor to the risk of cardiovascular events and death. In the year 2015, about 1.5 billion of adult people worldwide had hypertension (as defined by office systolic blood pressure ≥ 140 mmHg or office diastolic blood pressure ≥ 90 mmHg). Moreover, the number of hypertensive patients with age ranging from 30 to 79 years doubled in the last 30 years (from 317 million men and 331 million women in the year 1990 to 652 million men and 626 million women in 2019) despite stable age-standardized prevalence worldwide. Despite such impressive growth, the proportion of controlled hypertension is very low. A better understanding of the pathogenesis of hypertension may contribute to the development of innovative therapeutic strategies. In this context, alterations of the messenger RNA metabolism have been recently evaluated as contributors to the pathogenesis of hypertension, and pharmacological modulation of RNA metabolism is under investigation as potential and novel therapeutic armamentarium in hypertension.

After assessing the levels of spread and severity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, academic literature focused on the pathophysiology of coronavirus disease 2019 (COVID-19) [...]

Background: Serum uric acid predicts the onset and progression of kidney disease, and the occurrence of cardiovascular and all-cause mortality. Nevertheless, it is unclear which is the appropriate definition of hyperuricemia in presence of chronic kidney disease (CKD). Our goal was to study the independent impact of uric acid and CKD on mortality.Methods: We retrospectively investigated 21,963 patients from the URRAH study database. Hyperuricemia was defined on the basis of outcome specific cut-offs separately identified by ROC curves according to eGFR strata. The primary endpoints were cardiovascular and all-cause mortality.Results: After a mean follow-up of 9.8 year, there were 1,582 (7.20%) cardiovascular events and 3,130 (14.25%) deaths for all causes. The incidence of cardiovascular and all-cause mortality increased in parallel with reduction of eGFR strata and with progressively higher uric acid quartiles. During 215,618 person-years of follow-up, the incidence rate for cardiovascular mortality, stratified based on eGFR (>90, between 60 and 90 and

Background. The inadvertent lead malposition in the left heart (ILMLH) is an under-recognized event, which may complicate the implantation of cardiac electronic devices (CIEDs). Methods. We investigated the clinical conditions associated with ILMLH and the treatment strategies in these patients. We made a systematic review of the literature and identified 132 studies which reported 157 patients with ILMLH. Results. The mean age of patients was 68 years, and 83 were women. ILMLH was diagnosed, on average, 365 days after CIEDs implantation. Coexisting conditions were patent foramen ovale in 29% of patients, arterial puncture in 24%, perforation of the interatrial septum in 20%, atrial septal defect in 16% and perforation of the interventricular septum in 4%. At the time of diagnosis of ILMLH, 46% of patients were asymptomatic, 31% had acute TIA or stroke and 15% had overt heart failure. Overall, 14% of patients were receiving anticoagulants at the time of diagnosis of ILMLH. After diagnosis of ILMLH, percutaneous or surgical lead extraction was carried out in 93 patients (59%), whereas 43 (27%) received anticoagulation. During a mean 9-month follow-up after diagnosis of ILMLH, four patients experienced TIA or stroke (three on oral anticoagulant therapy and one after percutaneous lead extraction). Conclusion. ILMLH is a rare complication, which is usually diagnosed about one year after implantation of CIEDs. An early diagnosis of ILMLH is important. Lead extraction is a safe and effective alternative to anticoagulants.

Coronavirus disease 2019 (COVID-19) vaccines proved a strong clinical efficacy against symptomatic or moderate/severe COVID-19 and are considered the most promising approach for curbing the pandemic. However, some questions regarding the safety of COVID-19 vaccines have been recently raised. Among adverse events to vaccines and despite a lack of signal during phase III clinical trials, an increase in blood pressure (BP) after COVID-19 vaccination has been reported as a potential adverse reaction. We systematically analyze this topic and undertook a meta-analysis of available data to estimate the proportion of patients with abnormal BP or raise in BP after vaccination. Six studies entered the final analysis. Overall, studies accrued 357,387 subjects with 13,444 events of abnormal or increased BP. After exclusion of outlier studies, the pooled estimated proportion of abnormal/increased BP after vaccination was 3.20% (95% CI: 1.62–6.21). Proportions of cases of stage III hypertension or hypertensive urgencies and emergencies was 0.6% (95% CI: 0.1% to 5.1%). In conclusion, abnormal BP is not rare after COVID-19 vaccination, but the basic mechanisms of this phenomenon are still unclear and require further research.

The novel respiratory Syndrome Coronavirus-2 (SARS-CoV-2) caused a cluster of pneumonia cases in China at the end of 2019. After few months, it led to a pandemic that has spread throughout most countries of the world (https://coronavirus.jhu.edu/map.html).

Because of demographic aging, the prevalence of arterial hypertension (HTN) and cardiac arrhythmias, namely atrial fibrillation (AF), is progressively increasing. Not only are these clinical entities strongly connected, but, acting with a synergistic effect, their association may cause a worse clinical outcome in patients already at risk of ischemic and/or haemorrhagic stroke and, consequently, disability and death. Despite the well-known association between HTN and AF, several pathogenetic mechanisms underlying the higher risk of AF in hypertensive patients are still incompletely known. Although several trials reported the overall clinical benefit of renin–angiotensin–aldosterone inhibitors in reducing incident AF in HTN, the role of this class of drugs is greatly reduced when AF diagnosis is already established, thus hinting at the urgent need for primary prevention measures to reduce AF occurrence in these patients. Through a thorough review of the available literature in the field, we investigated the basic mechanisms through which HTN is believed to promote AF, summarising the evidence supporting a pathophysiology-driven approach to prevent this arrhythmia in hypertensive patients, including those suffering from primary aldosteronism, a non-negligible and under-recognised cause of secondary HTN. Finally, in the hazy scenario of AF screening in hypertensive patients, we reviewed which patients should be screened, by which modality, and who should be offered oral anticoagulation for stroke prevention.

Hypertension is the most frequent chronic and non-communicable disease all over the world, with about 1.5 billion affected individuals worldwide. Its impact is currently growing, particularly in low-income countries. Even in high-income countries, hypertension remains largely underdiagnosed and undertreated, with consequent low rates of blood pressure (BP) control. Notwithstanding the large number of clinical observational studies and randomized trials over the past four decades, it is sad to note that in the last few years there has been an impressive paucity of innovative studies. Research focused on BP mechanisms and novel antihypertensive drugs is slowing dramatically. The present review discusses some advances in the management of hypertensive patients, and could play a clinical role in the years to come. First, digital/health technology is expected to be increasingly used, although some crucial points remain (development of non-intrusive and clinically validated devices for ambulatory BP measurement, robust storing systems enabling rapid analysis of accrued data, physician-patient interactions, etc.). Second, several areas should be better outlined with regard to BP diagnosis and treatment targets. Third, from a therapeutic standpoint, existing antihypertensive drugs, which are generally effective and well tolerated, should be better used by exploiting available and novel free and fixed combinations. In particular, spironolactone and other mineral-corticoid receptor antagonists should be used more frequently to improve BP control. In particular, some drugs initially developed for conditions different from hypertension including heart failure and diabetes have demonstrated to lower BP significantly and should therefore be considered. Finally, renal artery denervation is another procedure that has proven effective in the management of hypertension.

Background: It is uncertain whether exposure to renin–angiotensin system (RAS) modifiers affects the severity of the new coronavirus disease 2019 (COVID-19) because most of the available studies are retrospective. Methods: We tested the prognostic value of exposure to RAS modifiers (either angiotensin-converting enzyme inhibitors [ACE-Is] or angiotensin receptor blockers [ARBs]) in a prospective study of hypertensive patients with COVID-19. We analyzed data from 566 patients (mean age 75 years, 54% males, 162 ACE-Is users, and 147 ARBs users) hospitalized in five Italian hospitals. The study used systematic prospective data collection according to a pre-specified protocol. All-cause mortality during hospitalization was the primary outcome. Results: Sixty-six patients died during hospitalization. Exposure to RAS modifiers was associated with a significant reduction in the risk of in-hospital mortality when compared to other BP-lowering strategies (odds ratio [OR]: 0.54, 95% confidence interval [CI]: 0.32 to 0.90, p = 0.019). Exposure to ACE-Is was not significantly associated with a reduced risk of in-hospital mortality when compared with patients not treated with RAS modifiers (OR: 0.66, 95% CI: 0.36 to 1.20, p = 0.172). Conversely, ARBs users showed a 59% lower risk of death (OR: 0.41, 95% CI: 0.20 to 0.84, p = 0.016) even after allowance for several prognostic markers, including age, oxygen saturation, occurrence of severe hypotension during hospitalization, and lymphocyte count (adjusted OR: 0.37, 95% CI: 0.17 to 0.80, p = 0.012). The discontinuation of RAS modifiers during hospitalization did not exert a significant effect (p = 0.515). Conclusions: This prospective study indicates that exposure to ARBs reduces mortality in hospitalized patients with COVID-19.

Background: Post-operative (POP) atrial fibrillation (AF) is frequent in patients who undergo cardiac surgery. However, its prognostic impact in the long term remains unclear. Methods: We followed 1386 patients who underwent cardiac surgery for an average of 10 ± 3 years. According to clinical history of AF before and after surgery, four subgroups were identified: (1) patients with no history of AF and without episodes of AF during the first 30 days after surgery (control or Group 1, n = 726), (2) patients with no history of AF before surgery in whom new-onset POP AF was detected during the first 30 days after surgery (new-onset POP AF or Group 2, n = 452), (3) patients with a history of paroxysmal/persistent AF before cardiac surgery (Group 3, n = 125, including 87 POP AF patients and 38 who did not develop POP AF), and (4) patients with permanent AF at the time of cardiac surgery (Group 4, n = 83). All-cause mortality was the primary outcome of the study. We tested the associations of potential determinants with all-cause mortality using univariable and multivariable statistical analyses. Results: Overall, 473 patients (34%) died during follow-up. After adjustment for multiple confounders, new-onset POP AF (hazard ratio (HR) = 1.31, 95% confidence interval (CI): 0.90–1.89; p = 0.1609), history of paroxysmal/persistent AF before cardiac surgery (HR = 1.33, 95% CI: 0.71–2.49; p = 0.3736), and permanent AF (Group 4) (HR = 1.55, 95% CI 0.82–2.95; p = 0.1803) were not associated with a significantly increased risk of mortality when compared with Group 1 (patients with no history of AF and without episodes of AF during the first 30 days after surgery). In new-onset POP AF patients, oral anticoagulation was not associated with mortality (HR = 1.13, 95% CI: 0.83–1.54; p = 0.4299). Conclusions: In this cohort of patients who underwent different types of heart surgery, POP AF was not associated with an increased risk of mortality. In this setting, the role of long-term anticoagulation remains unclear.

Background: Although severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may cause an acute multiorgan syndrome (coronavirus disease 2019 (COVID-19)), data are emerging on mid- and long-term sequelae of COVID-19 pneumonia. Since no study has hitherto investigated the role of both cardiac and pulmonary ultrasound techniques in detecting such sequelae, this study aimed at evaluating these simple diagnostic tools to appraise the cardiopulmonary involvement after COVID-19 pneumonia. Methods: Twenty-nine patients fully recovered from COVID-19 pneumonia were considered at our centre. On admission, all patients underwent 12-lead electrocardiogram (ECG) and transthoracic echocardiography (TTE) evaluation. Compression ultrasound (CUS) and lung ultrasound (LUS) were also performed. Finally, in each patient, pathological findings detected on LUS were correlated with the pulmonary involvement occurring after COVID-19 pneumonia, as assessed on thoracic computed tomography (CT). Results: Out of 29 patients (mean age 70 ± 10 years; males 69%), prior cardiovascular and pulmonary comorbidities were recorded in 22 (76%). Twenty-seven patients (93%) were in sinus rhythm and two (7%) in atrial fibrillation. Persistence of ECG abnormalities from the acute phase was common, and nonspecific repolarisation abnormalities (93%) reflected the high prevalence of pericardial involvement on TTE (86%). Likewise, pleural abnormalities were frequently observed (66%). TTE signs of left and right ventricular dysfunction were reported in two patients, and values of systolic pulmonary artery pressure were abnormal in 16 (55%, despite the absence of prior comorbidities in 44% of them). Regarding LUS evaluation, most patients displayed abnormal values of diaphragmatic thickness and excursion (93%), which correlated well with the high prevalence (76%) of pathological findings on CT scan. CUS ruled out deep vein thrombosis in all patients. Conclusions: Data on cardiopulmonary involvement after COVID-19 pneumonia are scarce. In our study, simple diagnostic tools (TTE and LUS) proved clinically useful for the detection of cardiopulmonary complications after COVID-19 pneumonia.

Background It is debated whether echocardiography should be part of the diagnostic workup in all hypertensive patients. We identified some factors potentially associated with left ventricular hypertrophy (LVH) at echocardiography in untreated hypertensive patients. Methods and Results We studied 2150 patients without LVH at ECG. All patients underwent standard 12‐lead ECG and echocardiography. Mean age was 48.7 years, and mean office blood pressure was 154/97 mm Hg. Prevalence of echocardiographic LVH (LV mass >47.0 g/m2.7 in women and >50.0 g/m2.7 in men) was 37.1%. We developed a nomogram based on 7 items (age, smoking, body mass index, office systolic and diastolic blood pressure, Cornell voltage, and chronic kidney disease) on the basis of a multivariable logistic regression analysis. We internally validated the model by bootstrap recalibration and obtained a calibration curve to assess agreement in the validation data set. Probability of LVH at echocardiography ranged from 90% (score, ≥180 points). Proportion of patients with LVH progressively increased with the total score (χ2=444.8; P136 in men and >124 in women.

Left ventricular (LV) hypertrophy at electrocardiography (ECG) predicts incident atrial fibrillation (AF). However, the diagnostic performance of ECG for diagnosis of LV hypertrophy in patients with AF is still not well characterized.We analyzed 563 hypertensive patients enrolled in the Umbria-Atrial Fibrillation (Umbria-FA) registry, an ongoing prospective observational registry in patients with AF. All patients underwent ECG and standard echocardiography at their entry in the Register. Mean age was 74 years and 43% of patients were women. Prevalence of ECG-LV hypertrophy, defined by Perugia criterion corrected for body mass index, was 23%. Echocardiographic LV mass was the reference standard. Sensitivity, specificity and diagnostic accuracy of ECG-LV hypertrophy were 37.4% (95% confidence interval [CI]: 31.6–43.4), 90.0% (95% CI: 86.0–93.2) and 64.5% (95% CI: 60.4–68.3), respectively. Performance was comparable in patients with AF or sinus rhythm at ECG recording. The area under the receiver-operating characteristic (ROC) curve was 0.622 (95% CI: 0.580–0.664) in the group with AF and 0.662 (95% CI: 0.605–0.720) in that with sinus rhythm (p ​= ​0.266 for comparison). These data suggest that standard ECG is reliable for diagnosis of LV hypertrophy in patients with a history of AF, regardless of the presence of AF or sinus rhythm at the time of ECG recording.

Abstract Background Valvular heart disease (VHD) and atrial fibrillation (AF) often coexist. Aim We investigated whether type 2 VHD (other than moderate-severe rheumatic mitral stenosis or mechanical heart valve) influences the prescription of anticoagulants in AF. Methods Umbria-Fibrillazione Atriale is a prospective multicenter registry in patients with AF. For the purpose of this study, type 2 VHD patients were propensity matched with non-VHD counterparts in a 1:1 ratio. Patients with type 1 VHD (moderate-severe mitral stenosis or mechanical heart valve) were excluded. Results We identified 2,212 patients with AF and excluded 46 because data on VHD were unavailable. Type 2 VHD was present in 426 patients (19.7%). Before registry entry visit, 77.1% of type 2 VHD and 66.8% of non-VHD patients were on anticoagulants. At discharge, 90.8 and 85.2% of patients, respectively, were on anticoagulants. After propensity-score matching, 386 patient-pairs were created. In the matched sample, the likelihood of being on anticoagulants before (odds ratio [OR]: 1.43, 95% confidence interval [CI]: 1.02–2.01, p = 0.036) and after (1.63, 95% CI: 1.04–2.57, p = 0.034) the entry visit was higher in type 2 VHD than in non-VHD patients. Patients with type 2 VHD were 70% more likely to receive vitamin K antagonists (VKAs) (OR: 1.70, 95% CI: 1.28–2.27, p

The data presented in this article are related to the research article entitled “Patients aged 90 years or older with atrial fibrillation treated with oral anticoagulants: A multicentre observational study” [1]. This article unveils original data of a cohort of 546 patients aged 90 years or older with non-valvular atrial fibrillation treated with oral anticoagulants. Here, we describe the time course of ischemic stroke and systemic embolism and of major bleeding according to the presence of outcome predictors and report the causes of permanent discontinuation and of death. Furthermore, we report data on the incidence of ischemic stroke and systemic embolism, of major bleeding, of permanent discontinuation and of all-cause death comparing i) oral anticoagulant naïve users vs. long-term oral anticoagulant users, ii) patients on anticoagulant therapy for less than 2 years (new users) vs. patients on anticoagulant therapy for more than 2 years. The material of this data article provides a better understanding on the use of oral anticoagulants in this fragile population and facilitates further critical analysis. Moreover, it aims at highlighting the importance of increasing knowledge in patients aged 90 years or older. These patients are often excluded from or under-represented in clinical trials and cohort studies.

Background Cardiac biomarkers and left ventricular hypertrophy (LVH) are related to the risk of stroke and death in patients with atrial fibrillation. We investigated the interrelationship between LVH and cardiac biomarkers and their independent associations with outcomes. Methods and Results Plasma samples were obtained at baseline in 5275 patients with atrial fibrillation in the RE‐LY (Randomized Evaluation of Long‐Term Anticoagulation Therapy) trial. NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), cardiac troponin I and T, and growth differentiation factor‐15 were determined using high‐sensitivity (hs) assays. LVH was defined by ECG. Cox models were adjusted for baseline characteristics, LVH, and biomarkers. LVH was present in 1257 patients. During a median follow‐up of 2.0 years, 165 patients developed a stroke and 370 died. LVH was significantly (P

BackgroundThe different geometric patterns of the left ventricle may or may not coexist with chamber dilatation. The prognostic impact of such a combination is unclear. Methods and ResultsWe studied a cohort of 2635 initially untreated patients with hypertension, mean age 50 years. At entry, 24‐hour ambulatory blood pressure progressively increased across the patterns of normal geometry, concentric left ventricular (LV) remodeling, eccentric nondilated LV hypertrophy (LVH), eccentric dilated LVH, concentric nondilated LVH, and concentric dilated LVH. During a mean follow‐up of 9.7 years, 360 patients developed a first major cardiovascular event at a rate (×100 patient‐years) of 1.41. The event rate was 0.93 in the group with normal LV geometry, 1.10 in the group with LV concentric remodeling, 1.40 in the group with nondilated eccentric LVH, 2.10 in the group with eccentric dilated LVH, 2.34 in the group with nondilated concentric LVH, and 4.67 in the group with dilated concentric LVH (log‐rank test: P

Background and objectives: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Among extra-pulmonary manifestations of COPD, atrial fibrillation (AF) is commonly observed in clinical practice. The coexistence of COPD and AF significantly affects the risk of cardiovascular morbidity and mortality. Nonetheless, the mechanisms explaining the increased risk of vascular events and death associated to the presence of COPD in AF are complex and not completely understood. We analyzed data from an Italian network database to identify markers and mediators of increased vascular risk among subjects with AF and COPD. Materials and Methods: Cross-sectional analysis of the Umbria Atrial Fibrillation (Umbria-FA) Registry, a multicenter, observational, prospective on-going registry of patients with non-valvular AF. Of the 2205 patients actually recruited, 2159 had complete clinical data and were included in the analysis. Results: the proportion of patients with COPD was 15.6%. COPD patients had a larger proportion of permanent AF when compared to the control group (49.1% vs. 34.6%, p < 0.0001) and were more likely to be obese and current smokers. Other cardiovascular risk factors including chronic kidney disease (CKD), peripheral artery disease and subclinical atherosclerosis were more prevalent in COPD patients (all p < 0.0001). COPD was also significantly associated with higher prevalence of previous vascular events and a history of anemia (all p < 0.0001). The thromboembolic and bleeding risk, as reflected by the CHA2DS2VASc and HAS-BLED scores, were higher in patients with COPD. Patients with COPD were also more likely to have left ventricular (LV) hypertrophy at standard ECG than individuals forming the cohort without COPD (p = 0.018). Conclusions: AF patients with COPD have a higher risk of vascular complications than AF patients without this lung disease. Our analysis identified markers and mediators of increased risk that can be easily measured in clinical practice, including LV hypertrophy, CKD, anemia, and atherosclerosis of large arteries.