Hard Outcomes Research Articles

Prognostication in NAFLD: physiological bases, clinical indicators, and newer biomarkers.

Non-alcoholic fatty liver disease (NAFLD) is becoming an epidemic in Western countries. Notably, while the majority of NAFLD patients will not evolve until advanced liver disease, a minority of them will progress towards liver-related events. Therefore, risk stratification and prognostication are emerging as fundamental in order to optimize human and economicresources for the care of these patients.Liver fibrosis has been clearly recognized as the main predictor of poor hepatic and extrahepatic outcomes. However, a prediction based only on the stage of fibrosis is near-sighted and static, as it does not capture the propensity of disease to further progress, the speed of progression and their changes over time. These determinants, which result from the interaction between genetic predisposition and acquired risk factors (obesity, diabetes, etc.), express themselves in disease activity, and can be synthesized by biomarkers of hepatic inflammation and fibrogenesis.In this review, we present the currently available clinical tools for risk stratification and prognostication in NAFLD specifically with respect to the risk of progression towards hard hepatic outcomes, i.e., liver-related events and death. We also discuss about the genetic and acquired drivers of disease progression, together with the physiopathological bases of their come into action. Finally, we introduce the most promising biomarkers in the direction of repeatedly assessing disease activity over time, mainly in response to future therapeutic interventions.

Association of Pharmacological Treatments and Hospitalization and Death in Individuals With Amphetamine Use Disorders in a Swedish Nationwide Cohort of 13 965 Patients

There are no medications approved by authorities for the treatment of amphetamine or methamphetamine dependence, and studies investigating the effectiveness of pharmacological treatments in hard outcomes, such as hospitalization and death, are lacking. To investigate the association between pharmacotherapies and hospitalization and mortality outcomes in persons with amphetamine or methamphetamine use disorder. This nationwide register-based cohort study was conducted from July 2006 to December 2018 with a median (IQR) follow-up time of 3.9 (1.0-6.1) years. Data were analyzed from December 1, 2021, to May 24, 2022. All residents aged 16 to 64 years living in Sweden with a registered first-time diagnosis of amphetamine or methamphetamine use disorder and without previous diagnoses of schizophrenia or bipolar disorder were identified from nationwide registers of inpatient care, specialized outpatient care, sickness absence, and disability pension. Medications for substance use disorders (SUDs) or for attention-deficit/hyperactive disorder, mood stabilizers, antidepressants, benzodiazepines and related drugs, and antipsychotics. Medication use vs nonuse was modeled with the PRE2DUP (from prescription drug purchases to drug use periods) method. Primary outcomes were hospitalization due to SUD and any hospitalization or death, which were analyzed using within-individual models by comparing use and nonuse periods of 17 specific medications or medication classes in the same individual to minimize selection bias. The secondary outcome was all-cause mortality, studied using between-individual analysis as traditional Cox models. There were 13 965 individuals in the cohort (9671 [69.3%] male; mean [SD] age, 34.4 [13.0] years). During follow-up, 7543 individuals (54.0%) were taking antidepressants, 6101 (43.7%) benzodiazepines, 5067 (36.3%) antipsychotics, 3941 (28.2%) ADHD medications (1511 [10.8%] were taking lisdexamphetamine), 2856 (20.5%) SUD medications, and 1706 (12.2%) mood stabilizers. A total of 10 341 patients (74.0%) were hospitalized due to SUDs, 11 492 patients (82.3%) were hospitalized due to any cause or died, and 1321 patients (9.5%) died of any cause. Lisdexamphetamine was the only medication in this study that was significantly associated with a decrease in risk of 3 outcomes (adjusted hazard ratio [aHR], 0.82; 95% CI, 0.72-0.94 for SUD hospitalization; aHR, 0.86; 95% CI, 0.78-0.95 for any hospitalization or death; aHR, 0.43; 95% CI, 0.24-0.77 for all-cause mortality). Methylphenidate use also was associated with lower all-cause mortality (aHR, 0.56; 95% CI, 0.43-0.74). Use of benzodiazepines was associated with a significantly higher risk of SUD hospitalization (aHR, 1.17; 95% CI, 1.12-1.22), any hospitalization or death (aHR, 1.20; 95% CI, 1.17-1.24), and all-cause mortality (aHR, 1.39; 95% CI, 1.20-1.60). Use of antidepressants or antipsychotics was associated with a slight increase in risk of SUD hospitalization (aHR, 1.07; 95% CI, 1.03-1.11 and aHR, 1.05; 95% CI, 1.01-1.09) as well as any hospitalization or death (aHR, 1.10; 95% CI, 1.06-1.14 and aHR, 1.06; 95% CI, 1.03-1.10, respectively). In this study, use of lisdexamphetamine was associated with improved outcomes in persons with amphetamine or methamphetamine use disorders, encouraging the conduct of randomized clinical trials. Prescription benzodiazepine use was associated with poor outcomes.

Hyperchloremia and mortality in the ICU: a prospective cohort study

Introduction: Part of the interventions in patients admitted to intensive care units (ICU) consist of the administration of crystalloids, implying a risk for the development of side effects. One of these is hyperchloremia, linked to the appearance of metabolic acidemia and systemic inflammatory response. Given these findings, observational studies have been developed, trying to establish an association between hyperchloremia and outcomes such as mortality and kidney failure; however, its diverse results prompt the development of new studies. In Colombia, there are no prospective cohort studies that establish any type of association with hard outcomes. Goal. To determine the association between the development of hyperchloremia and mortality and acute renal failure, in patients hospitalized in the ICU, in two hospitals in Bogotá D.C. Methodology: Analytical prospective cohort study conducted between June 1, 2019 and August 31, 2021. Results: 325 patients were analyzed, the cumulative incidence of hyperchloremia and acute renal failure in the entire study population was 44.6% and 29.5%, respectively. The cumulative incidence of death in the exposed was 36.5% vs 23.3% in the unexposed, with a relative risk RR=1.57, (95% CI 1.11-2.2) (p=<0.001). The cumulative incidence of acute renal failure was 43.4% in exposed patients and 18.3% in non-exposed patients, with a RR=2.37 with a (95% CI 1.65-3.4) (p<0.001). Conclusion: There is an association between the development of hyperchloremia and the outcomes of mortality and acute renal failure in critically ill patients.

Abstract 11823: Are Disease-Specific Patient-Reported Outcomes Measures (PROMs) Used in Cardio Genetics? A Review

Background: Besides hard medical outcomes in patients with inherited cardiac conditions (ICC). it is crucial to focus on the patient-reported outcomes (PRO) as well. These patients may have a disease-specific need due to ICC-related distress concerning family members and reproductive choices. We evaluated which PRO scales are currently used in cardiogenetics. Methods: From three datasets (PubMed, PsychINFO, and Web of Science), eligible studies published between 2008-2022 were selected as described in the review protocol (PROSPERO 2021 CRD42021271384). The quality of studies was assessed (https://pubmed.ncbi.nlm.nih.gov/27082055 ) and analyzed for the primary outcome variable of patient-reported outcomes. Results: Eighteen out of 232 articles were selected for data extraction; 9 studies used a cross-sectional design, and population characteristics and outcome measures varied. The risk of bias was high or unclear in 77% of the studies. All studies mainly used two questionnaires in combination or alone: the short form of medical outcomes survey (SF-36), a generic PROM that reports on health status and the Hospital Anxiety and Depression Scale (HADS), a standard measure of psychological well-being. Thirteen studies using SF-36 showed lower scores on the mental health component in patients with ICC versus population norms. Ten studies using HADS showed a prevalence of clinically significant anxiety (17-47%) and depression (8.3% to 28%) which are higher than the population norm (8.3% and 6.3%). Conclusion: Our results from only a few published studies indicate that although psychological morbidity in ICC patients is high, measurements are non-specific, variable, and generic and address overall health, instead of addressing factors specific to ICC, such as heritability. We propose to develop a disease-specific PROM for cardiogenetics to evaluate the heritability factor in patients with ICC to implement in the care pathway and optimize patient-centred care.

Abstract 13512: Patiromer to Manage Hyperkalemia in Patients Receiving Optimized Renin-Angiotensin-Aldosterone System Inhibitors for Heart Failure (DIAMOND): Prespecified Analysis of Patients With Hyperkalemia or Previous Hyperkalemia

Introduction: Renin-angiotensin-aldosterone system inhibitors (RAASis) are central to the treatment of heart failure with reduced ejection fraction (HFrEF); hyperkalemia (HK) or fear of HK often leads to suboptimal RAASi use. In the DIAMOND trial, 85% of patients with HFrEF and HK (serum potassium [sK + ] ≥5.0 mEq/L) or previous HK, which had led to RAASi discontinuation, achieved optimal RAASi and mineralocorticoid receptor antagonist (MRA) doses with open label run-in patiromer treatment. The benefit of using patiromer in patients with current HK vs a history of HK is unknown. Methods: Patients with HFrEF and either present HK or previous HK entered a single-blinded run-in phase ≤12 weeks to optimize RAASi while receiving patiromer; then were randomized (1:1) double-blind to continue with patiromer, or patiromer withdrawal (placebo). The primary endpoint was the mean change in sK + from baseline (BL) to the end of study. Secondary endpoints were: sK + >5.5 mEq/L, durable enablement of MRA at target dose, adverse events (AEs) of HK, HK-related hard outcomes, and a win ratio of novel RAASi use score. This prespecified analysis was conducted in patients with HK or with previous HK. Results: Of 1195 patients entering the run-in phase, 878 were randomized, of whom 354 (40%) had HK on study entry and 524 (60%) had normokalemia at BL. Of patients with HK (83.9%) and patients with previous HK (85.3%) achieved patiromer-facilitated RAASi optimization during the run-in. Patiromer consistently controlled sK + in patients both groups. A greater effect of patiromer on maintaining MRA at target dose, was seen in patients with HK versus those with previous HK. Conclusion: In patients with HFrEF, patiromer can effectively control sK + and facilitate the optimization of MRA use, this may be of most benefit to patients with HK.

Treatment response in recent-onset heart failure with reduced ejection fraction: non-ischaemic vs. ischaemic aetiology.

In heart failure (HF) with reduced left ventricular ejection fraction (HFrEF), the prognosis appears better in non-ischaemic than in ischaemic aetiology. Infrequent diagnostic work-up for ischaemic heart disease (IHD) in HF is reported. In this study, we compared short-term response to initiated guideline-directed medical treatment (GDMT) in recent-onset HFrEF of non-ischaemic (non-IHF) vs. ischaemic (IHF) aetiology and evaluated the frequency of coronary investigation. Patients hospitalized with recent-onset HFrEF [left ventricular ejection fraction (LVEF)<40%] between 1 January 2016 and 31 December 2019 were included. Treatment response was determined by use of a hierarchical clinical composite outcome classifying each patient as worsened, improved, or unchanged based on hard outcomes (mortality, heart transplantation, and HF hospitalization) and soft outcomes (±≥10 unit change in LVEF, ±≥30% change in N-terminal pro-B-type natriuretic peptide, and ±≥1 point change in New York Heart Association functional class) during 28weeks of follow-up. The associations between baseline characteristics and composite changes were analysed with multiple logistic regression. Among the 364 patients analysed, 47 were not investigated for IHD. Comparing non-IHF (n=203) vs. IHF (n=114), patients were younger (mean age 61.0 vs. 69.4years, P<0.001) with lower mean LVEF (26% vs. 31%, P<0.001), but with similar male predominance (70.4% vs. 75.4%, P=0.363). For non-IHF vs. IHF, the composite outcomes were worsened (19.1% vs. 43.9%, P<0.001) and improved (74.2% vs. 43.9%, P<0.001). After multivariable adjustments, IHF was associated with increased odds for worsening [odds ratio (OR) 2.94; 95% confidence interval (CI) 1.51-5.74; P=0.002] and decreased odds for improvement (OR 0.35; 95% CI 0.18-0.65; P<0.001). In cases without previous IHD or new-onset myocardial infarction (n=261), a decision for coronary investigation was made in 69.0%. In recent-onset HFrEF, patients with non-IHF responded better to GDMT than patients with IHF. Almost one-third of patients selected for follow-up at HF clinics were never investigated for IHD.

Novel Drugs for Diabetes Also Have Dramatic Benefits on Hard Outcomes of Heart and Kidney Disease.

Diabetes is a major risk factor for developing cardiovascular disease. Patients with both diabetes and cardiovascular disease have even higher mortality. The convergence of cardiology and diabetology therapy is an important step in treating patients and advancing research. Major landmark trials and meta-analyses involving Sodium Glucose Cotransporter 2 inhibitors have shown dramatic clinical cardiorenal benefits in patients both with and without type 2 diabetes. In type 2 diabetes patients, Glucagon-like peptide-1 receptor agonists have been shown to improve major cardiac outcomes. This hot topic of research and clinical use of glucose lowering drugs intersects the fields of cardiovascular, renal, and diabetic medicine. The numerous cardiorenal benefits have led to the rapid adoption in clinical guidelines of these glucose lowering drugs in patients with Type 2 diabetes, cardiovascular disease, or renal disease.

A Systematic Review and Meta-Analysis of Robot-Assisted Mitral Valve Repair.

Robot-assisted surgery is a minimally invasive approach for repairing the mitral valve. This study aimed to assess its safety and clinical efficacy when compared with conventional sternotomy, partial sternotomy, and right minithoracotomy. A systematic review of peer-reviewed studies comparing robot-assisted mitral valve repair with conventional sternotomy, partial sternotomy, and right minithoracotomy was conducted following Cochrane Collaboration guidelines. Meta-analyses were performed where possible. The search strategy yielded 15 primary studies, of which 12 compared robot-assisted with conventional sternotomy, 2 compared robot-assisted with partial sternotomy, and 6 compared robot-assisted with right minithoracotomy. The overall quality of evidence was low, and there was a lack of data on long-term outcomes. Individual studies and pooled data demonstrated that robotic procedures were comparable to conventional sternotomy and other minimally invasive approaches with respect to the rates of stroke, renal failure, reoperation for bleeding, and mortality. Robot-assisted mitral valve repair was superior to conventional sternotomy with reduced atrial fibrillation, intensive care unit and hospital stay, pain, time to return to normal activities, and physical functioning at 1 year. However, robot-assisted mitral valve repair had longer cardiopulmonary, aortic cross-clamp, and procedure times compared with all other surgical approaches. Based on current evidence, robot-assisted mitral valve repair is comparable to other approaches for safety and early postoperative outcomes, despite being associated with longer operative times. Ideally, future studies will be randomized controlled trials that compare between robot-assisted surgery, conventional surgery, and other minimally surgery approaches focusing on hard clinical outcomes and patient-reported outcomes.

From the Editor’s Desk...

In non-alcoholic fatty liver disease (NAFLD), the risk of disease progression and the incidence of hard clinical outcomes are not well established at the population level. Allen et al. performed a study including 5,123 adults diagnosed with NAFLD between 1996 and 2016 in Olmsted county, Minnesota, who were followed for a median of 6.4 years for liver-related outcomes and death. The study found that the risk of progression from NAFLD to cirrhosis was 3% in 15 years, from compensated cirrhosis to first decompensation was 33% in 4 years (8%/year), and from first decompensation to subsequent decompensation was 47% in 2 years.

Efficacy and safety of proprotein covertase subtilisin/kexin type 9 inhibitors among patients with acute coronary syndrome: a meta-analysis of randomized controlled trials

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have formed part of the armamentarium of lipid-lowering therapy, most especially low-density lipoprotein-cholesterol (LDL-C) reduction, which in turn decreases the risk of atherosclerotic cardiovascular diseases and adverse cardiovascular events. However, studies are sparse on the benefit of initiating PCSK9 inhibitors during the early phase of an acute coronary sydrome (ACS). Purpose The objective of this meta-analysis is to investigate the efficacy and safety of the PCSK9 inhibitors evolocumab and alirocumab in the acute setting of an ACS. Methods A systematic search for randomized controlled trials (RCTs) that involve the use of PCSK9 inhibitors in ACS was done using MEDLINE/PubMed and Cochrane Library. Results Three RCTs (n=385 participants) were included in this meta-analysis comparing PCSK9 inhibitors versus placebo in patients hospitalized for ACS. Among patients being managed for ACS, PCSK9 inhibitors demonstrated a greater reduction in LDL-C compared to placebo as early as day 3 (WMD −41.65%, 95% CI [−60.09, −23.21], p&amp;lt;0.00001), and was maintained until week 4 (WMD −45.67%, 95% CI [−64.82, −26.53], p&amp;lt;0.00001). The occurrence of adverse events did not significantly differ between the two groups in terms of hospitalization for recurrent ACS (OR 0.99, 95% CI 0.10–9.98, p=1.0), hospitalization for heart failure (OR 6.18, 95% CI 0.26–146.78, p=0.26), or cerebrovascular events (OR 3.12, 95% CI 0.31–31.30, p=0.33). Conclusion In patients admitted for ACS, the early administration of PCSK9 inhibitors such as evolocumab and alirocumab during the first 24 hours of hospitalization resulted in a rapid and significant reduction of LDL-C without any significant adverse event as compared to placebo. Further validation of the role of PCSK9 inhibitors in the setting of ACS is needed to robustly investigate its contribution in improving hard cardiovascular outcomes. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): St. Luke's Medical Center Global City

Cumulative hyperinsulinemia, hyperglycaemia, and insulin resistance from mid-adolescence through young adulthood with carotid intima-media thickness progression: a 9-year longitudinal study

Abstract Background In a recent meta-analysis of randomized clinical trials conducted among adults, carotid intima-media thickness (cIMT) progression was established as a predictor of cardiovascular morbidity and mortality. However, due to the paucity of hard outcomes among adolescents and young adults, a single cIMT measure has largely been used as a marker of preclinical atherosclerotic changes. The repeated measure of cIMT in the young population is scarce thus a knowledge gap exists on the associations of metabolic indices with cIMT progression. Purpose To investigate the associations of cumulative fasting plasma glucose, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) with cIMT progression in adolescence. Methods We studied 1779 British 15-year-olds (50% females) followed up for 9 years. Fasting insulin and glucose were measured in line with standard protocols at ages 15, 17, and 24 years, respectively. HOMA-IR was computed for each time point. Metabolic indices were age and sex-specifically dichotomized as ≥75%, indicating high category and &amp;lt;75% indicating moderate or reference category. cIMT from the right and left common carotid arteries at 17 years was assessed by ultrasound using a linear 12-MHz transducer (Vivid7, GE Medical, Chicago, Illinois) and cIMT from the right and left common carotid arteries at 24 years was measured using an ultrasound machine (CardioHealth Panasonic and a 13.5 MHz linear array broadband transducer (probe; centre frequency 9.0 MHz). We conducted linear mixed-effect model analyses and adjusted for statistically significant determinants of cIMT progression, viz: sex, age, high sensitivity C-reactive protein, insulin or glucose, dual-energy Xray absorptiometry measured total fat mass and lean mass, systolic blood pressure, diastolic blood pressure, smoking status, and ActiGraph measured sedentary time and light physical activity. Covariates were repeatedly measured. Results Participants mean (SD) age in years at different time points were 15.43 (0.29), 17.69 (0.31), and 24.53 (0.72). Cumulative high exposures to glucose: effect estimate 0.009 mm [95% CI −0.003 to 0.021; p=0.130], insulin: 0.002 mm [−0.030 to 0.013; p=0.704], and HOMA-IR: 0.003 mm [−0.009 to 0.016; p=0.608] from 15 to 24 years of age were not associated with the 7-year cIMT progression after full covariate adjustments. Sex-based analyses were consistent with the group analyses in both males and females. Conclusion These findings suggest that hyperinsulinemia, hyperglycaemia, and elevated insulin resistance from mid-adolescence through young adulthood may not be associated with progressive carotid wall thickening during late adolescence through young adulthood. Future studies investigating the role of other metabolic indices such as cumulative elevated lipid exposures on cIMT progression in the young population are warranted. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Finnish Cultural Foundation

Collaterals and extent of myocardial injury in patients with acute coronary syndromes – an analysis of the prospective SPUM-ACS cohort

Abstract Introduction The impact of collateral circulation in the presence of severe coronary artery disease such as chronic total occlusion (CTO) has been extensively studied, with results despite few discrepancies, supporting an overall benefit on preservation of myocardial tissue and left ventricular ejection fraction (LVEF). However, less is known about the protective effects of collaterals in the context of acute coronary syndromes (ACS). In the current study we sought to analyze the incidence, grade and impact of collateral circulation in a large prospectively recruited cohort of patients presenting with ACS with independent events adjudication. Methods and results 4'546 ACS patients presenting with ACS, enrolled in the prospective Special Program University Medicine ACS (SPUM-ACS) cohort were included. The current analysis showed the presence of a collateralized culprit lesion in 12.9% (n=586) of patients, 84% (n=492) originating from the contralateral side and 16% (n=94) from the ipsilateral side. Of those 64.6% (n=378) were being graded as Rentrop 2 or more. There were no differences in baseline characteristics between the two groups including incidence of diabetes, coronary artery disease, age and gender. However, despite the presence of collaterals graded Rentrop 2 or more, those patients had a significantly lower LVEF mean 48,44% vs 51.6%, p=0.025 and higher creatinine Kinase levels, mean (CK) 981 U/I vs 957 UI, p&amp;lt;0.001 as compared to patients with absent collateral-circulation on admission. Interestingly a sub analysis of the STEMI population showed no significant differences in both LVEF and CK at presentation, while troponin (TNT) plasma levels were significantly lower in patients with collaterals (mean TNT 0.0031 ug/l vs 0.035 ug/l p=0.001). Additionally no differences in cardiovascular mortality, stent thrombosis or MI was seen at one year follow-up. Conclusion The current analysis highlights a possible protective impact of a pre-existing collateral circulation against myocardial injury in the setting of ACS and ST elevation myocardial infarction. However this was not translated into improvement in hard outcomes acutely and up to one year of follow up, but may be important in the long run. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Swiss National Research Foundation - ZurichHeart House

Exercise oscillatory ventilation disturbances: finding order amongst chaos

Abstract Background Exercise Oscillatory Ventilation (EOV) during Cardiopulmonary Exercise Test (CPET) predicts prognosis in patients with Heart Failure (HF). In these patients, O2 consumption (VO2) oscillations have also been described, possibly secondary to circulatory delay. We hypothesize that in clinically meaningful EOV, cardiac output variation is mirrored by VO2 oscillation, which is then chronologically followed by a similar oscillation in minute ventilation (VE) (Figure 1). Accordingly, we aimed to assess whether this new definition surpassed that of classical EOV. Methods This is a single-centre cohort study of consecutive patients undergoing CPET from 2016 to 2018. Patients with LVEF &amp;gt;50% were excluded. CPET was performed on a treadmill to the limit of tolerance. Data was collected as a rolling average of 20 seconds and a composite VE/time and VO2/time plot was created. Classical EOV was defined as three or more regular oscillations of the VE graph with a minimal average amplitude of five litters. The addition of exercise VO2-to-VE peak-to-peak ventilation asynchrony (EVA) to the previous criteria fulfilled the new definition. The primary endpoint was a composite of time to all-cause death, heart transplantation or HF hospitalization. Results Overall, 177 patients were enrolled (mean age 58±11 years, LVEF 34±9%), of whom 35 had EOV and 17 had EVA. Compared to those without EVA, patients with EVA had markers of more severe HF. During a median follow-up of 32 (21–42) months, 55 patients met the primary outcome (32 all-cause deaths, 15 heart transplants, 47 HF hospitalizations). In multivariate analysis, EVA was associated with a 2.5-fold increased risk of events (HR 2.489; 95% CI: 1.302–4.759; p=0.006), adjusted for peak VO2, VE to CO2 production ratio (VE/VCO2 slope) and LVEF. EVA outperformed EOV in predicting the primary endpoint at 1 year, with a similar sensitivity and higher specificity (96.2 vs. 83.2%). The rate of events between the subgroup of patients without EVA was similar regardless of presence of EOV, contrasting with a higher rate in the EVA subgroup (Figure 2). Conclusion EVA is a strong predictor of hard outcomes in a broad population with HF. The new definition may outperform that of classical EOV. The incidence and prognostic value of EVA in the management algorithm and risk stratification of patients with HF is worth being further explored. Funding Acknowledgement Type of funding sources: None.

Blood pressure telemonitoring and telemedicine for hypertension management—positions, expectations and feasibility of Latin–American practitioners. SURVEY carried out by several cardiology and hypertension societies of the Americas

Purpose To assess the opinion of Latin–American physicians on remote blood pressure monitoring and telehealth for hypertension management. Material and methods Cross-sectional survey of physicians residing in Latin–America. The study was conducted by the Mexico Hypertension Experts Group, Interamerican Society of Hypertension, Interamerican Society of Cardiology Epidemiology and Cardiovascular Prevention Council, and National Cardiologist Association of Mexico. An online survey composed of 40 questions using Google Forms was distributed from 7 December 2021, to 3 February 2022. The survey was approved by the GREHTA Ethics Committee and participation was voluntary and anonymous. Multiple logistic regression models were constructed to identify the challenges of telehealth. Results 1753 physicians’ responses were gathered. The responses came from physicians from different Latin–American countries, as follows: 24% from Mexico, 20.6% from Argentina, 14.7% from Colombia, 10.9% from Brazil, 8.7% from Venezuela, 8.2% from Guatemala and 3.2% from Paraguay. Responders with a high interest in carrying out their assistance task through remote telemonitoring reached 48.9% (821), while 43.6% are already currently conducting telemonitoring. A high number, 62%, claimed to need telemonitoring training. There is a direct relation between higher interest in telemonitoring and age, medical specialty, team working, residence in the biggest cities, expectations regarding telemedicine and reimbursement. Conclusions Remote monitoring is feasible in Latin–America. General practitioners and specialists from bigger cities seem eager and are self-perceived as well-trained and experienced. Facilities and resources do not seem to be a challenge but training reinforcement and telemedicine promotion is necessary for those physicians less motivated. PLAIN LANGUAGE SUMMARY What is the context? Hypertension is one of the leading worldwide modifiable risk factors for premature death. Strong evidence supports that effective treatment of this condition results in a significant reduction of hard outcomes. Only 20%–30% of hypertensive patients are within the blood pressure targets recommended by guidelines in Latin–America. There is an urgent need to implement innovative strategies to reverse this alarming health situation. What is new? Latin–American physicians were highly predisposed to telemonitoring practice. This high motivation was not influenced by hardware or software availability, technological knowledge or experience, by volume of monthly consultations, or by area (private–public) where the care activity is carried out. This high motivation may be supported by the conviction that this practice could be very useful as a complement to face–to–face assistance and a highly effective tool to improve adherence even though respondents considered that just 10% of the patients would prefer telemonitoring over office consultation. What is the impact? Facilities and resources do not seem to be a challenge but training reinforcement and telemedicine promotion is necessary for those physicians less motivated. The general perception is that it is necessary to move forward to resolve legal gaps and financial aspects. Physicians must adapt to changes and develop new communication strategies in a world where the unrestricted access to teleinformation makes patients self-perceived as experts.

Serum Calcification Propensity Represents a Good Biomarker of Vascular Calcification: A Systematic Review.

Vascular calcification contributes to cardiovascular morbidity and mortality. A recently developed serum calcification propensity assay is based on the half-transformation time (T50) from primary calciprotein particles (CPPs) to secondary CPPs, reflecting the serum’s endogenous capacity to prevent calcium phosphate precipitation. We sought to identify and review the results of all published studies since the development of the T50-test by Pasch et al. in 2012 (whether performed in vitro, in animals or in the clinic) of serum calcification propensity. To this end, we searched PubMed, Elsevier EMBASE, the Cochrane Library and Google Scholar databases from 2012 onwards. At the end of the selection process, 57 studies were analyzed with regard to the study design, sample size, characteristics of the study population, the intervention and the main results concerning T50. In patients with primary aldosteronism, T50 is associated with the extent of vascular calcification in the abdominal aorta. In chronic kidney disease (CKD), T50 is associated with the severity and progression of coronary artery calcification. T50 is also associated with cardiovascular events and all-cause mortality in CKD patients, patients on dialysis and kidney transplant recipients and with cardiovascular mortality in patients on dialysis, kidney transplant recipients, patients with ischemic heart failure and reduced ejection fraction, and in the general population. Switching from acetate-acidified dialysate to citrate-acidified dialysate led to a longer T50, as did a higher dialysate magnesium concentration. Oral administration of magnesium (in CKD patients), phosphate binders, etelcalcetide and spironolactone (in hemodialysis patients) was associated with a lower serum calcification propensity. Serum calcification propensity is an overall marker of calcification associated with hard outcomes but is currently used in research projects only. This assay might be a valuable tool for screening serum calcification propensity in at-risk populations (such as CKD patients and hemodialyzed patients) and, in particular, for monitoring changes over time in T50.

Thiazide diuretics are back in CKD: the case of chlorthalidone.

Sodium and volume excess is the fundamental risk factor underlying hypertension in chronic kidney disease (CKD) patients, who represent the prototypical population characterized by salt-sensitive hypertension. Low salt diets and diuretics constitute the centrepiece for blood pressure control in CKD. In patients with CKD stage 4, loop diuretics are generally preferred to thiazides. Furthermore, thiazide diuretics have long been held as being of limited efficacy in this population. In this review, by systematically appraising published randomized trials of thiazides in CKD, we show that this class of drugs may be useful even among people with advanced CKD. Thiazides cause a negative sodium balance and reduce body fluids by 1-2l within the first 2-4weeks and these effects go along with improvement in hypertension control. The recent CLICK trial has documented the antihypertensive efficacy of chlorthalidone, a long-acting thiazide-like diuretic, in stage 4 CKD patients with poorly controlled hypertension. Overall, chlorthalidone use could be considered in patients with treatment-resistant hypertension when spironolactone cannot be administered or must be withdrawn due to side effects. Hyponatremia, hypokalaemia, volume depletion and acute kidney injury are side effects that demand a vigilant attitude by physicians prescribing these drugs. Well-powered randomized trials assessing hard outcomes are still necessary to more confidently recommend the use of these drugs in advanced CKD.

Association between urinary sodium excretion and hard outcomes in non-dialysis chronic kidney disease patients

BackgroundRestriction of sodium intake is routinely recommended for patients with chronic kidney disease (CKD). Whether or not sodium intake is associated with the progression of CKD and mortality remains uncertain. We evaluated the association between urinary sodium excretion (as a surrogate for sodium intake) with the occurrence of renal failure and mortality in patients with non-dialytic CKD.MethodsWe conducted a retrospective study of patients followed at a CKD clinic care hospital from October 2006 to March 2017. Adult patients with non-dialytic CKD were included. Using a time-to-event analysis, we examined the association of urinary sodium excretion as a categorical variable (categorized as quintiles: 1st quintile: 0.54–2.51 g; 2nd quintile: 2.52–3.11 g, 3rd quintile: 3.12–3.97 g, 4th quintile: 3.98–5.24 g and 5th quintile: 5.26–13.80 g) and the outcomes of interest. The primary outcome was defined as progression to end-stage renal disease requiring any type of renal replacement therapy. The secondary outcome was mortality.ResultsTwo hundred five patients were included in the study (mean follow up of 2.6 years) with a mean eGFR of 26 (19–41) ml/min/1.73m2. 37 patients (18%) required renal replacement therapy and 52 (25,3%) died. There was association between urinary sodium excretion and need for renal replacement therapy (adjusted HR 0.245; 95%CI 0.660–0.912). There was no association between urinary sodium excretion and mortality in adjusted models.ConclusionModerate sodium intake was associated with a lower risk of renal failure.

Glycated albumin is associated with all-cause and cardiovascular mortality among U.S. adults with and without diabetes: A retrospective cohort study

Background and aimsGlycated albumin (GA) reflects short-term glycemic control, but few data are available on its association with hard clinical outcomes. The purpose of this study is to evaluate the association between GA levels and all-cause and cardiovascular mortality in people with and without a previous diagnosis of diabetes. Methods and resultsSerum GA levels were measured in 12147 people from the general population (1319 with and 10828 without diabetes) that participated in the 1999–2004 cycles of the National Health and Nutrition Examination Survey (NHANES). We evaluated the association between GA and all-cause and cardiovascular mortality through December 2015 by linking NHANES data with data from the National Death Index. Associations were compared with those observed for hemoglobin A1c (HbA1c). After a median follow-up of 13 years, 2785 participants (619 with and 2166 without diabetes) died, 651 of cardiovascular causes. Multivariable-adjusted Cox proportional hazard models showed that higher baseline GA levels were significantly associated with a higher incidence of both outcomes in participants with (all-cause: HR 1.03, 95% CI 1.01-1.04; cardiovascular: HR 1.04, 95% CI 1.02-1.07) and without diabetes (all-cause: HR 1.05, 95% CI 1.03-1.08; cardiovascular: HR: 1.08, 95% CI 1.02-1.14); on the other hand, we found a trend for increased mortality with increasing HbA1c levels in patients with known diabetes, but not in participants without. ConclusionsFor a novel measure of hyperglycemia to be considered useful, its association with hard, long term clinical outcomes is of great importance. We showed that GA is associated with mortality in the general population independently of a previous diagnosis of diabetes.

The "FIFTY SHADOWS" of the RALES Trial: Lessons about the Potential Risk of Dietary Potassium Supplementation in Patients with Chronic Kidney Disease.

Hyperkalaemia (HK) is one of the most common electrolyte disorders and a frequent reason for nephrological consultations. High serum potassium (K+) levels are associated with elevated morbidity and mortality, mainly due to life-threatening arrhythmias. In the majority of cases, HK is associated with chronic kidney disease (CKD), or with the use of renin–angiotensin–aldosterone system inhibitors (RAASis) and/or mineral corticoid antagonists (MRAs). These drugs represent the mainstays of treatment in CKD, HF, diabetes, hypertension, and even glomerular diseases, in consideration of their beneficial effect on hard outcomes related to cardiovascular events and CKD progression. However, experiences in relation to the Randomised Aldactone Evaluation Study (RALES) cast a long shadow that extends to the present day, since the increased risk for HK remains a major concern. In this article, we summarise the physiology of K+ homeostasis, and we review the effects of dietary K+ on blood pressure and cardiovascular risk in the general population and in patients with early CKD, who are often not aware of this disease. We conclude with a note of caution regarding the recent publication of the SSaSS trial and the use of salt substitutes, particularly in patients with a limited capacity to increase K+ secretion in response to an exogenous load, particularly in the context of “occult” CKD, HF, and in patients taking RAASis and/or MRAs.

Prevalence and Predictors of Abdominal Aorta Calcification in Patients With Psoriasis-A Case Control Study.

BackgroundPsoriasis is associated with a high prevalence of cardiovascular disease in Caucasians, but only a few studies from sub-Saharan Africa have investigated the prevalence of cardiovascular disease in patients with psoriasis. Abdominal aortic calcification (AAC) is a strong predictor of future cardiovascular events and all-cause mortality in the general population. We investigated the prevalence and risk factors for AAC in a predominantly non-Caucasian cohort of South African patients with psoriasis.MethodsA cross-sectional case-control study of adult psoriasis patients (n = 69) and controls (n = 80), matched for gender, ethnicity and body mass index, attending tertiary Dermatology and Rheumatology clinics in Johannesburg, South Africa. Demographic, anthropometric, clinical and biochemical data were recorded. All participants underwent non-contrast abdominal CT scans. Images were assessed for AAC at the supra-coeliac aorta, supra-mesenteric aorta and aortic bifurcation using Horos DICOM viewer software.ResultsAbdominal aortic calcification at any site was more prevalent in the psoriasis than control group (47.8% vs 22.5%, p < 0.005). The aortic bifurcation was the commonest site for AAC in both groups, but more prevalent in the psoriasis group (42.0% vs 21.3%, p < 0.005). The psoriasis group was also more likely to smoke, have hypertension and type 2 diabetes (56.5% vs 25.0%, p < 0.005; 72.0% vs 55.0%, p < 0.005; 24.6% vs 3.80%, p < 0.0005, respectively). Multivariable logistic regression analysis demonstrated that age, smoking and type 2 (T2DM) diabetes were independently associated with AAC (odds ratio (95% CIs): 1.16 (1.07, 1.20), 4.30 (2.15, 8.61) and 3.45 (1.09, 15.7) respectively), but psoriasis was not. Forward regression analysis demonstrated that smoking attenuated the association of psoriasis with AAC.ConclusionOur findings show AAC to be more common in psoriasis patients compared to controls. Age, T2DM and smoking were independent predictors of AAC. Smoking cessation is essential in psoriatic patients to reduce the risk of cardiovascular events. The clinical utility of AAC detection by CT imaging to risk stratify for hard cardiovascular outcomes needs to be explored.