Established Cardiovascular Disease Research Articles

Effects of a New Group of Antidiabetic Drugs in Metabolic Diseases.

The prevalence of type 2 diabetes mellitus (T2DM) is rising in the general population. This increase leads to higher cardiovascular risk, with cardiovascular diseases being the main cause of death in diabetic patients. New therapeutic weapons for diabetes mellitus are now available. Sodium-glucose cotransporter type 2 (SGLT2) inhibitors are novel drugs that are widely used due to their strong benefit in preventing hospitalization for decompensated heart failure and renal protection, limiting the deterioration of the glomerular filtration rate, independently of the presence of diabetes mellitus. These drugs have also shown benefit in the prevention of atherosclerotic cardiovascular events and cardiovascular mortality in diabetic patients with established cardiovascular disease. On the other hand, patients with T2DM usually present a high burden of associated comorbidities. Some of these entities are arterial hypertension, dyslipidemia, hyperuricemia, obesity, non-alcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), vascular aging, respiratory diseases, or osteoporosis and fractures. Healthcare professionals should treat these patients from an integral point of view, and not manage each pathology separately. Therefore, as potential mechanisms of SGLT2 inhibitors in metabolic diseases have not been fully reviewed, we conducted this review to know the current evidence of the use and effect of SGLT2 inhibitors on these metabolic diseases.

CELESTIA: Cost-Effectiveness Analysis of Empagliflozin Versus Sitagliptin in Patients with Type 2 Diabetes in Greece.

Globally, the prevalence of diabetes is on the rise, with the number of affected individuals predicted to cross 700 million by 2045. In Greece, in 2015, almost 700,000 people received prescribed medication for type 2 diabetes. The CELESTIA study aims to assess the cost-effectiveness of empagliflozin compared to branded sitagliptin in type 2 diabetes patients both with and without established cardiovascular disease in Greece from a third payer perspective. The IQVIA Core Diabetes Model was used and analyses were conducted from the Greek healthcare payer perspective. Patients received either empagliflozin or sitagliptin until HbA1c threshold of 8.5% (69 mmol/mol) was exceeded. Subsequently, patients were assumed to intensify to insulin therapy. Baseline cohort characteristics and treatment effects were derived from clinical trial data. Literature data were used for input (utilities, treatment costs and costs of diabetes-related complications costs). A lifetime time horizon (50 years) was applied, and costs and benefits were discounted at an annual rate of 3.5%. Over a lifetime horizon, for empagliflozin, the estimated ICER was of €6,587 and €966 per quality-adjusted life years gained versus sitagliptin, in patients without established cardiovascular disease and in patients with established cardiovascular disease, respectively. Probabilistic sensitivity analysis confirmed the robustness of the analysis. The analysis demonstrated that for type 2 diabetes patients, empagliflozin is a cost-effective treatment option versus branded sitagliptin in Greece.

Real-world impact of empagliflozin on total cost of care in adults with type 2 diabetes: Results from an outcomes-based agreement.

BACKGROUND: Value-based health care is expanding through payment models such as outcomes-based agreements between manufacturers and payers. OBJECTIVE: To describe the total-cost-of-care outcomes of an outcomes-based agreement evaluating the real-world impact of empagliflozin vs other type 2 diabetes mellitus (T2DM) drugs among all patients with T2DM, with and without cardiovascular disease (within and beyond the requirement of the agreement). METHODS: In this prospective real-world analysis, members from the health plan of an integrated health care delivery system from the commercial and Medicare Advantage lines of business, who qualify under the confines of the contract, were included for analysis. Thus, members aged 18 years and older who were continuously enrolled in the identification (January 1, 2018, to December 31, 2018) and measurement periods (≤1 year post-index) with a T2DM diagnosis were retained. Patients using empagliflozin and empagliflozin-combination drugs constituted the empagliflozin group; those using all other antihyperglycemics, the nonempagliflozin group. Patients with type 1 diabetes, or those using metformin or insulin monotherapy, at index were excluded. Eligible members were followed for up to the earliest occurrence of disenrollment date, discontinuation (60-day medication fill gap allowed) of empagliflozin (or nonempagliflozin containing) medication, or the end of the measurement period. We compared, using Student's t-test and summary statistics (for reporting the outcomes agreement) and a propensity-matched difference-in-difference model (for the followup evaluation beyond the requirement of the agreement), the mean all-cause total cost of care (pharmacy plus medical) per patient per month (PPPM) between the 2 groups, including a subgroup of members with a baseline cardiovascular disease diagnosis. RESULTS: There were 4,577 (3,069 and 1,508 in the commercial and Medicare) and 33,712 (15,571 and 18,141 in the commercial and Medicare) in the empagliflozin and nonempagliflozin groups, respectively. The difference in mean total cost PPPM was $75 lower for empagliflozin vs nonempagliflozin groups, driven mainly by lower medical costs in the empagliflozin group (-$465 PPPM). However, the difference was not statistically significant in the propensity score-matched model. CONCLUSIONS: Although empagliflozin had higher pharmacy costs, the total cost of care for patients with T2DM and with established cardiovascular disease were comparable to the group of patients with all other T2DM, driven mainly by lower medical costs. DISCLOSURES: The authors report no conflicts of interest beyond being employees of the 2 organizations involved in this outcomes-based agreement. Ms. Palli is a former employee of Boehringer Ingelheim Pharmaceuticals, Inc., who was affiliated at the time of study conduct.

Improving cardiovascular health behaviors through a comprehensive lifestyle intervention program during the pandemic in India

Abstract Funding Acknowledgements Type of funding sources: None. Background We have witnessed a dramatic dip in adherence to cardiovascular health behaviors during the COVID-19 pandemic. Data from across the globe has shown that risk factors for cardiovascular disease (CVD) such as decreased physical activity, poor diet, and increased depression, loneliness, and stress have peaked during the pandemic. Having been badly affected by the pandemic and having had prolonged periods of countrywide lockdown, the at-risk and established CVD population has faced a major challenge in adhering to a healthy lifestyle in India. Purpose This study aimed to analyze the change in cardiovascular health behaviors brought about by a comprehensive lifestyle intervention program (CLIP) during the pandemic in India. Methods All at-risk and CVD patients who had participated in the CLIP from mid 2020 to mid 2022 and had completed the internally validated health behavior assessment questionnaire, pre and post-program, were included in this retrospective study. A multidisciplinary team consisting of Physician, Physiotherapist, Dietician, and Counseling Psychologist provided the sessions online and/or in-person for the home-based and hybrid programs respectively. When a combination of online and in-person sessions were provided for a subject, it was called a hybrid program. The core components of the CLIP were exercise training, education on relevant health topics, nutritional guidance and psychosocial counseling. Results Age of the subjects (n=50) at enrolment was 54±13 years and 40 (80%) were male. The time between pre-program and post-program assessments was 110 (IQR 47) days. Number of at-risk and CVD patients attending home-based and hybrid programs are shown in the Figure. There were 4 couples in the study cohort; 21 (50%) of the remaining 42 subjects had at least 1 other family member attend the majority of sessions. There was a significant improvement in all the cardiovascular health behaviors, namely adequate daily intake of fruits, vegetables and whole grains, choice of heart-healthy foods between meals, sufficient weekly exercise and a reduction in self-reported chronic stress, upon completion of the CLIP (Table). Conclusions A comprehensive lifestyle intervention program that incorporates a multipronged approach to behavior modification is effective in improving cardiovascular health behaviors in individuals at-risk as well as with established cardiovascular disease in India. The ripple effect of behavior modification in the accompanying family members needs to be studied systematically.

Left atrial late gadolinium enhancement in patients with ischaemic stroke.

To evaluate the extent of left atrial (LA) fibrosis in patients with a recent stroke without atrial fibrillation and controls without established cardiovascular disease. This prospectively designed study used cardiac magnetic resonance to detect LA late gadolinium enhancement as a proxy for LA fibrosis. Between 2019 and 2021, we consecutively included 100 patients free of atrial fibrillation with recent ischaemic stroke (<30 days) and 50 age- and sex-matched controls. LA fibrosis assessment was achieved in 78 patients and 45 controls. Blinded to the cardiac magnetic resonance results, strokes were adjudicated according to modified Trial of Org 10172 in Acute Stroke Treatment classification as undetermined aetiology (n = 42) or as attributable to large- or small-vessel disease (n = 36). Patients with stroke had a larger extent of LA fibrosis [6.9%, interquartile range (IQR) 3.6-15.4%] than matched controls (4.2%, IQR 2.3-7.5%; P = 0.007). No differences in LA fibrosis were observed between patients with stroke of undetermined aetiology and those with large- or small-vessel disease (6.6%, IQR 3.8-16.0% vs. 6.9%, IQR 3.4-14.6%; P = 0.73). LA fibrosis was more extensive in patients with stroke than in age- and sex-matched controls. A similar extent of LA fibrosis was observed in patients with stroke of undetermined aetiology and stroke classified as attributable to large- or small-vessel disease. Our findings suggest that LA structural abnormality is more frequent in patients with stroke than in controls independent of aetiological classification.

Acute myocardial infarction during late COVID-19 era: patient characteristics, presentation and outcomes.

COVID-19 pandemic has unquestionably influenced care of acute myocardial infarction (AMI). Still, its impact on patients (pts) characteristics, presentation, treatment, and outcomes remains not well established in late pandemic times. To address this issue, we performed a prospective study of type-1 AMI pts admitted in a tertiary care hospital. Pts were enrolled during 6-months in 2019 (n=122; pre-COVID-19 (PC) group) and in 2021 (n=196; late-COVID-19 (C) group). Data was based on pts interview and review of medical records. Age and gender distribution, as well as ST/Non-ST-Elevation Myocardial Infarction (STEMI/NSTEMI) proportion and access to coronariography and revascularization were similar between groups. C pts presented more pre-existing established cardiovascular disease (CVD) (43% vs 30%; p=0,03); more frequent description of typical chest pain (94% vs 84%; p=0,002); higher levels of pain intensity, in a 0-10 scale (8±2 vs 7±2; p=0,02); higher frequencies of AMI complications (27% vs 15%; p=0,01) and worse Killip (K) class evolution (K≥2 in 22% C vs 13% PC pts; p=0,05). In conclusion, late pandemic AMI pts presented worse in-hospital outcomes in our study, though pre-hospital and hospital care were comparable to pre-pandemic times. Covid pts had a higher burden of pre-existing established CVD and a more typical and intense symptom presentation. Therefore, it can be hypothesized that "sicker" pts continued to look for help when presenting AMI symptoms, while "less sick" pts and the ones with less typical and intense symptoms possibly avoided contact with health care services during late pandemic period.

Plasma levels of CCL21, but not CCL19, independently predict future coronary events in a prospective population-based cohort

Background and aimsThe homeostatic chemokines CCL21 and CCL19 have been explored as biomarkers in cardiovascular disease prediction in patients with established cardiovascular disease, but associations between these chemokines and first-time coronary event incidence have not been investigated before. Here, we explored associations between CCL21 or CCL19 and first-time incident coronary events in the general population-based Malmö Diet and Cancer cohort with two decades of follow-up. MethodsCCL21 and CCL19 levels in plasma were analysed with ELISA and proximity extension assay and associations with disease incidence were explored with conditional logistic regression in a nested case-control cohort (CCL21; n = 676) and with Cox regression in a population-based cohort (CCL19; n = 4636). ResultsHigh CCL21 levels in plasma were associated with incident first-time coronary events independently of traditional risk factors (odds ratio of 2.64 with 95% confidence interval 1.62–4.31, p < 0.001, comparing the highest versus the lowest tertile of CCL21), whereas CCL19 was not. CCL19 was, however, associated with incident heart failure, as well as increased all-cause, cardiovascular and cancer mortality independently of age and sex. ConclusionsEven though CCL21 and CCL19 both signal through CCR7, these chemokines may not be interchangeable as disease predictors and CCL21 could be used for prediction of future coronary events in individuals without any previous coronary heart disease history.

Generalizability of the REDUCE-IT trial to South Asians with cardiovascular disease

South Asians (SAs) represent ∼25% of the world's population and account for >50% of global cardiovascular (CV) deaths, yet they continue to be underrepresented in contemporary clinical trials. The REDUCE-IT study demonstrated in a high-risk and predominantly White population that icosapent ethyl (IPE) lowered major adverse cardiovascular events by 25%. We sought to determine the generalizability of these results to a high-risk population of SAs with established CV disease living in Canada. This was a cross-sectional observational study of 200 statin-treated SAs (≥45 years) with atherosclerotic CV disease (ASCVD) (NCT05271591). SA ethnicity was self-identified as being of Anglo-Indian, Bangladeshi, Bengali, Bhutanese, Goan, Gujarati, Indian, Jatt, Kashmiri, Maharashtrian, Malayali, Nepali, Pakistani, Punjabi, Sindhi, Sinhalese, Sri Lankan, Tamil, Telugu, or other SA. ASCVD was defined as the presence of coronary, carotid, or peripheral atherosclerosis. Mean age of the cohort was 67 years, where 82% were men and 57% had diabetes. The predominant ASCVD phenotype was coronary artery disease (94%). Mean (SD) baseline LDL-C and triglycerides were 1.70 (0.8) mmol/L and 1.42 (1.0) mmol/L, respectively. Three-quarters were on high-intensity statin therapy. According to the Health Canada/Canadian Cardiovascular Society Guidelines and FDA-approved indication, 33% and 25% of the participants were, respectively, eligible for IPE. A large proportion of high-intensity, statin-treated, high-risk patients with ASCVD and of self-reported SA ethnicity are eligible for IPE. These data have important translational implications for SAs who are at a disproportionately higher risk of CV morbidity and mortality. This study was funded by an unrestricted grant provided by HLS Therapeutics Inc, Canada.

Adverse pregnancy outcomes and the development of short-term maternal cardiovascular disease risk factors

Adverse pregnancy outcomes (APOs) are linked to future maternal cardiovascular disease (CVD) risk factors and events. We sought to examine the association between APOs and short-term established CVD risk factors in a contemporary, high-risk, racially, and ethnically diverse hospital population in North Carolina.

Clinical Profile and In-Hospital Outcome of COVID-19 Infection among Patients with Cardiovascular Disease: A Cross-Sectional Study

Introduction: Coronary heart disease, hypertension, heart failure, diabetes, and other cardiovascular diseases (CVDs) increase the disease severity and in-hospital mortality among patients with COVID-19. Methods: This is a hospital-based study assessing the effects of CVD on the in-hospital outcomes in patients admitted with COVID-19. Clinical characteristics and in-hospital outcomes were studied in patients with cardiovascular risk factors and underlying CVD. Results: A total of 108 covid positive patients had an underlying cardiovascular disease/s in various forms with a mean age of 60.69±16.24 years and 55.6% were male. Hypertension and diabetes mellitus were the commonest cardiovascular risk factors. Among these patients, acute decompensated heart failure and cardiac arrhythmia commonly atrial fibrillation were the common cardiac complications. The in-hospital mortality rate was 16.67%. Those who died due to cardiac involvement was 18.2% in comparison to 14.3% of the patients who did not have cardiac involvement, although this could not reach statistical significance. The most common cause of death was multiorgan failure resulting in 44.5% of all cause of death followed by acute respiratory distress syndrome accounting 27.8% and refractory cardiogenic shock with 22.2% involvement. Among those who died vs those who survived length of hospital stay was significantly longer in death group (13.6 days vs 9.11 days, p=0.002) Conclusion: In patients hospitalized with COVID-19, pre-existing established cardiovascular risk factors and CVD appear to be important contributors to mortality. The involvement of multiorgan predisposes COVID-19 patients to accentuated risk of mortality.

Effects of the Sodium-Glucose Cotransporter Inhibitors on Cardiovascular Death and All-Cause Mortality: A Systematic Review and Meta-analysis of Randomized Placebo-Controlled Clinical Trials.

Patients with diabetes mellitus are at an increased risk of cardiovascular morbidity and all-cause mortality. Heart failure and type 2 diabetes often occur concomitantly, and each disease independently increases the risk for the other. Emerging data have revealed that some sodium-glucose cotransporter inhibitors (SGLTi) improve cardiovascular and renal outcomes, particularly in patients with type 2 diabetes. The magnitude of this effect in patients without any underlying condition remains unclear. As a result, we conducted a meta-analysis of the mortality outcomes of available SGLTi in patients with or without cardiovascular diseases, type 2 diabetes, cardiovascular risk factors, and heart failure. We performed a systematic review and meta-analysis of randomized, placebo-controlled major cardiovascular outcome trials of SGLTi in patients regardless of their cardiovascular disease or risk status. PubMed, Cochrane, Google Scholar, MEDLINE, and EMBASE were searched for the relevant studies. Three reviewers extracted study data and three reviewers summarized the strength of the evidence. Efficacy outcomes included all-cause mortality, major adverse cardiovascular events (myocardial infarction, stroke, or cardiovascular death), the composite of all-cause mortality, cardiovascular death, or hospitalization for heart failure. Odds ratios with 95% confidence intervals were pooled across trials to calculate the overall effect size. A total of 5043 all-cause mortality events were observed in the study groups. In 42,050 patients who received SGLTi, 2581 events were reported, and 2462 events were reported in 35,491 patients who received placebo (odds ratio = 0.86, 95% confidence interval 0.80-0.93, p = 0.0003). The use of SGLTi significantly reduced cardiovascular mortality compared with control across the patients' population (odds ratio = 0.86, 95% confidence interval 0.79-0.93, p = 0.0001). There was a consistent pattern of mortality beneficial estimates for all patients with different co-morbid conditions in the SGLTi-treated arm compared with the placebo-treated group. The presence or absence of significant cardiovascular disease risk factors (including a family history of premature coronary artery disease, baseline estimated glomerular filtration rate, dyslipidemia, hypertension, smoking, history of cardiovascular disease, and older age) did not affect the estimated mortality benefits. Sodium-glucose cotransporter inhibitorssignificantly reduced major adverse cardiovascular events, including hospitalization and all-cause mortality in patients with or without established atherosclerotic cardiovascular disease. We observed a beneficial trend in patients with heart failure with preserved ejection fraction, and no benefits in patients with stroke or myocardial infarction.

Statins Use in Patients with Cardiovascular Diseases and COVID-19 Outcomes: An Italian Population-Based Cohort Study.

The role of statins among patients with established cardiovascular diseases (CVDs) who are hospitalized with COVID-19 is still debated. This study aimed at assessing whether the prior use of statins was associated with a less severe COVID-19 prognosis. Subjects with CVDs infected with SARS-CoV-2 and hospitalized between 20 February 2020 and 31 December 2020 were selected. These were classified into two mutually exclusive groups: statins-users and non-users of lipid-lowering therapies (non-LLT users). The relationship between statins exposure and the risk of Mechanical Ventilation (MV), Intensive Care Unit (ICU) access and death were evaluated by using logistic and Cox regressions models. Of 1127 selected patients, 571 were statins-users whereas 556 were non-LLT users. The previous use of statins was not associated with a variation in the risk of need of MV (Odds Ratio [OR]: 1.00; 95% Confidence Intervals [CI]: 0.38-2.67), ICU access (OR: 0.54; 95% CI: 0.22-1.32) and mortality at 14 days (Hazard Ratio [HR]: 0.42; 95% CI: 0.16-1.10). However, a decreased risk of mortality at 30 days (HR: 0.39; 95% CI: 0.18-0.85) was observed in statins-users compared with non-LLT users. These findings support the clinical advice for patients CVDs to continue their treatment with statins during SARS-CoV-2 infection.

706 ETIOLOGICAL ROLE OF STRESS IN ACUTE CORONARY SYNDROME: THE STRESS-ACS-ACTION STUDY

Abstract Background Acute coronary syndrome (ACS) is the main cause of mortality worldwide and despite the adherence to guidelines it is still burdened by an unacceptable risk for cardiovascular (CV) events recurrence, highlighting the need to identify other than traditional cardiovascular risk factors (CVrF) implicated in atherosclerotic plaque instability. In this regard, psychosocial stress appears to be a crucial player in the development of CV disease. Nevertheless, stress is not easy to standardize and the mechanisms by which it promotes coronary artery disease (CAD) are poorly understood. Materials and Methods We therefore prospectively enrolled patients with ACS, stable coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) and subjects presenting traditional CVrF but without established CV disease. Multimodality cortisol assessment, expression of acute and chronic stress, through blood, urine and hair samples collection was ascertained at baseline. A regression analysis was performed to assess the relationships between significant variables at univariate analysis. Results Fifty patients were enrolled in the present study. Cortisol levels in blood and urine were numerically higher in patients with ACS compared to CAD patients and subjects with traditional CVrF only. Hair cortisol levels did not differ between the three groups. The regression analysis showed an inverse correlation (R= -,532, p&amp;lt;0.001 and R=-,615, p&amp;lt;0.001 respectively) between urinary cortisol (UC) and UC/creatinine ratio and left ventricular ejection fraction (LVEF). Conclusion The preliminary results of our study showed that patients with ACS did not have significantly higher levels of hair cortisol compared to stable patients. The finding of an inverse relationship between higher UC, UC/C ratio levels and lower LVEF values support a link between a hyperactivity of the hypothalamic-pituitary-adrenal axis and a worse ACS presentation. These preliminary data will be implemented with serial multimodality assessment of cortisol that allow potential implications in diagnosis and outcome.

Comparison of gliclazide vs linagliptin on hypoglycemia and cardiovascular events in type 2 diabetes mellitus: A systematic review.

Cardiovascular outcome trials have demonstrated cardiovascular safety of glimepiride (a sulfonylureas) against dipeptidyl peptidase-4 inhibitor linagliptin. Gliclazide (another newer sulfonylureas) has shown similar glycemic efficacy and 50% decreased risk of hypoglycemia compared to glimepiride. Considering the absence of cardiovascular outcome trials for gliclazide, we decided to conduct a systematic review of the literature to assess the car-diovascular (CV) safety by assessing the risk for major adverse CV events and hypoglycemia risk of gliclazide vs linagliptin in patients with type 2 diabetes (T2D). This systematic review followed the current Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to analyze all the clinical studies published from 2008 that compared the two drugs in patients with T2D with no risk of CV disease (CVD). We included only evidence designated high quality by the Oxford Center for Evidence-based Medicine-Levels of Evidence. Eight clinical studies were included in the narrative descriptive analysis (gliclazide: 5 and linagliptin: 3). The CV safety of gliclazide in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation trial and of linagliptin in the Cardiovascular and Renal Microvascular Outcome Study With Linagliptin (CARMELINA) and CARdiovascular Outcome study of LINAgliptin vs glimepiride in patients with T2D (CAROLINA) trials were excluded from the comparative analysis as these trials demonstrated CV and hypoglycemia benefits in patients at high risk of CVD. However, since these are landmark trials, they were discussed in brief to show the CV benefits and low hypoglycemia risk of gliclazide and linagliptin. We did not find any study comparing gliclazide with linagliptin. Hence, direct comparison of their major adverse CV events and hypoglycemia risk could not be carried out. However, the literature meeting the inclusion criteria showed that both drugs were effective in achieving the desired glycemic control and had low major adverse CV events and hypoglycemia risk in adult patients with no history of CVD. Gliclazide can be considered an effective and safe glucose-lowering drug in T2D patients with no established CVD but at high risk of CVD due to their T2D status. Future randomized controlled trials comparing gliclazide with linagliptin or dipeptidyl peptidase-4 inhibitors can confirm these findings.

769 EFFECT OF GLUCOSE LOWERING AGENTS ON CARDIAC AUTONOMIC FUNCTION AND STRUCTURE IN TYPE 2 DIABETES MELLITUS

Effects of novel glucose-lowering agents on cardiac autonomic function and structure in type 2 diabetes Ilaria Cavallari, Ernesto Maddaloni, Francesco Veneziano, Carla Indennidate, Maria Valeria Giaccari, Dario Tuccinardi, Silvia Pieralice, Nicola Napoli, Raffaella Buzzetti, Francesco Grigioni Background Novel glucose-lowering agents, such as sodium glucose co-transporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, have the potential to reduce major adverse cardiovascular events among people with type 2 diabetes. However, mechanisms behind their cardiovascular protection and the implications of positive chronotropic effects of GLP-1 receptor agonists are not fully understood. Purpose To elucidate and compare the effects of novel glucose-lowering agents on cardiac autonomic function and structure. Methods This prospective observational study included subjects with type 2 diabetes and either a history of established cardiovascular disease or multiple risk factors and early initiation (within 2 weeks) of a SGLT-2 inhibitor or a GLP-1 receptor agonist on top of standard of care. Patients were followed for a median of 2 months. As per study protocol, background medical therapy should have remained stable for the entire duration of the study. Cardiac autonomic reflex tests (heart rate response to a deep breathing and to standing) and echocardiography were performed in all patients at baseline and at the end of follow-up. Endpoints were changes from baseline of E/I ratio, 30:15 ratio and indices of cardiac structure and function. Results A total of 37 patients completed follow-up, of whom 20 were on SGLT-2 inhibitors and 17 on GLP-1 receptor agonists. Mean age was 69 years, mean disease duration was 14 years and mean HbA1c value was 7.5%. Cardiac autonomic dysfunction, defined as at least an abnormal test, was found in 19% of patients (n=7). At a median follow-up of 2 months, there were no differences from baseline in heart rate response to a deep breathing test (p=0.92) and to standing (p=0.86). No differences were found when patients were stratified according to drug class. Among echocardiographic parameters, significant reductions of left ventricular mass (300.5±73.3 vs 280.4±68.3 g/m2, p=0.048) and left atrial volume (61.3±29.4 vs 54.7±18.0 ml, p=0.034) were found with no interaction by drug class. Left ventricular end-diastolic and systolic volumes, ejection fraction, filling pressures and pulmonary artery pressure did not substantially change. Conclusions In a population of patients with type 2 diabetes, short-term treatment with novel glucose-lowering agents significantly reduced left ventricular mass and left atrial volume but did not affect cardiac autonomic function.

The efficacy of PDE5 inhibitors in diabetic patients.

Phosphodiesterase 5 inhibitors (PDE5i), since their introduction in the late 1990s, have proven their efficacy in treating several conditions, predominantly pulmonary hypertension and erectile dysfunction where they remain the first-line therapeutic option. However, in the recent years, growing evidence from both animal and human studies has emerged to suggest the additional benefits of PDE5i in cardiovascular and metabolic disorders. This is of specific interest to the diabetes population where prevalent cardiovascular disease and metabolic dysregulation significantly contribute to the increased morbidity and mortality. To examine the available data on the non-standard, pleiotropic effects of PDE5i in patients with diabetes mellitus. The review of the published background research, preclinical studies and clinical trials. In human studies, PDE5 inhibition appeared to be associated with reduced cardiovascular mortality and overall improved clinical outcomes in those with established cardiovascular disease. PDE5i were also consistently found to reduce albuminuria in subjects with diabetic nephropathy. Furthermore, animal data suggest a plausible effect of this group of medication on sensory function and neuropathic symptoms in diabetic neuropathy as well as improved wound healing. A decrease in insulin resistance and augmentation of beta cell function seen in preclinical studies has not been consistently demonstrated in human trials. In animal models, PDE5 inhibition appears to decrease oxidative stress and reduce some of the micro- and macrovascular complications associated with diabetes. However, data from human trials are limited and largely inconsistent, highlighting the need for adequately powered, randomised-controlled trials in diabetic cohorts in order to fully assess the benefits of PDE5i in this group of patients.

Assessment of microvesicles from different cell origins in patients with psoriasis: evidence of thrombogenic, proinflammatory microenvironment in the absence of established cardiovascular disease.

Psoriasis is associated with increased cardiovascular risk. Endothelial, platelet, and erythrocyte microvesicles (MVs) are novel biomarkers of endothelial dysfunction and thromboinflammation. We explored whether MVs of different cell types are elevated in patients with psoriasis, and investigated potential associations with disease severity and macrovascular function. Endothelial, platelet and erythrocyte MVs were measured using a standardized flow cytometry protocol in psoriasis patients and controls free from established cardiovascular disease. Carotid intima-media thickness (IMT) and pulse wave velocity (PWV) were measured as markers of subclinical atherosclerosis and arterial stiffness. Psoriasis severity was assessed with PASI (Psoriasis Area Severity Index). Both platelet (p < 0.001) and erythrocyte MVs (p = 0.046), yet not endothelial MVs, were significantly increased in patients with psoriasis (n = 41) compared with controls (n = 41). Patients with higher PASI (≥10) presented significantly higher levels of ErMVs compared to those with lower PASI (<10) (p = 0.047). Carotid IMT and PWV were comparable between psoriasis patients and controls and did not significantly correlate with MVs. In the multivariate analysis, psoriasis was identified as an independent predictor of both platelet (p < 0.001) and erythrocyte MVs (p = 0.043), while hypertension was independently associated with endothelial MVs (p < 0.001). Increased formation of platelet and erythrocyte MVs may be evident in psoriasis patients and is indicative of prothrombotic, proinflammatory microenvironment, even in the absence of subclinical macrovascular dysfunction and before the clinical onset of overt cardiovascular complications. Potential mechanistic links and prognostic implications of increased MVs in psoriasis warrant further investigation.

Rationale and design of the Effects of intensive Systolic blood Pressure lowering treatment in reducing RIsk of vascular evenTs (ESPRIT): A multicenter open-label randomized controlled trial

Lowering blood pressure (BP) effectively reduces the risk of cardiovascular (CV) events in high CV risk individuals. The optimal target of BP lowering among high CV risk individuals remains unclear. The Effects of intensive Systolic blood Pressure lowering treatment in reducing RIsk of vascular evenTs (ESPRIT) trial is a multi-center, open-label, randomized controlled trial to compare the efficacy and safety of intensive BP lowering strategy (Systolic BP target <120 mm Hg) and standard BP lowering strategy (Systolic BP target <140 mm Hg). Participants aged at least 50 years old with baseline systolic BP within 130 to 180 mm Hg at high CV risk, defined by established CV diseases or 2 major CV risk factors, were enrolled. The primary outcome is a composite CV outcome of myocardial infarction, coronary or non-coronary revascularization, hospitalization or emergency department visit from new-onset heart failure or acute decompensated heart failure, stroke, or death from CV diseases. Secondary outcomes include components of the primary composite outcome, all-cause death, a composite of the primary outcome or all-cause death, kidney outcomes, as well as cognitive outcomes. Despite of the interruption of COVID-19 outbreak, the ESPRIT trial successfully enrolled and randomized 11,255 participants from 116 hospitals or primary health care institutions. The mean age of the participants was 64.6 (standard deviation [SD], 7.1) years, 4,650 (41.3%) were women. Among them 28.9%, 26.9% and 38.7% had coronary heart disease, prior stroke and diabetes mellitus, respectively. COVID-19 outbreak affected the BP lowering titration process of the trial, and delayed the reach of BP target. The ESPRIT trial will address the important question on the optimal BP lowering target for individuals with high CV risk, and generate high quality evidence for treating millions of patients from East Asian countries.

Factors affecting prescription of sodium-glucose co-transporter 2 inhibitors in patients with type 2 diabetes mellitus with established cardiovascular disease/ chronic kidney disease in Hong Kong: a qualitative study

BackgroundSodium-glucose co-transporter 2 inhibitors (SGLT2 I) has cardiorenal protective properties and are recommended for patients with diabetes and established atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD). Although cardiorenal complications are high in diabetes and pose a significant financial burden on the Hong Kong health care system, the use of SGLT2 I in these populations remains low. And yet this issue has not been explored in Hong Kong primary care. This study aimed to explore factors affecting primary care doctors’ prescribing of SGLT2 I in patients with diabetes and established ASCVD/CKD in Hong Kong.MethodsA phenomenological qualitative research using semi-structured interviews was conducted between January and May 2021 in one Hospital Authority cluster in Hong Kong. Purposive sampling was employed to recruit primary care doctors in the cluster. The Theoretical Domains Framework (TDF) underpinned the study and guided the development of the interview questions. Data was analysed using both inductive and deductive approaches. The Consolidated criteria for reporting qualitative research (COREQ) checklist was used to guide the reporting.ResultsInterviews were conducted with 17 primary care doctors. Four overarching themes were inductively identified: knowledge and previous practice patterns influence prescription, balancing risks and benefits, doctors’ professional responsibilities, and system barriers. The four themes were then deductively mapped to the nine specific domains of the TDF: knowledge; intention; memory; beliefs about capabilities; beliefs about consequences; goals; role and identity; emotion; and environmental constraints. Most interviewees, to varying extent, were aware of the cardio-renal advantages and safety profile of SGLT2 I but are reluctant to prescribe or change their patients to SGLT2 I because of their knowledge gap that the cardio-renal benefits of SGLT2 I was independent of glyacemic efficacy. Other barriers included their considerations of patients’ age and renal impairment, and patients’ perceptions and preferences.ConclusionsDespite evidence-based recommendations of the utilisation of SGLT2 I in patients with established ASCVD/CKD, the prescription behaviour among primary care doctors was affected by various factors, most of which were amendable. Our findings will inform the development of structured interventions to address these factors to improve patients’ cardio-renal outcomes.

Most Recent Trials and Advances in Hypertension.

Hypertension is one of the most prevalent cardiovascular risk factors and blood pressure control remains a clinical challenge, especially for patients with established cardiovascular disease. Late-breaking clinical trials and other evidence in hypertension have evolved to assess the most accurate ways to measure blood pressure, the use of combination therapies, considerations in special populations and evaluation of new techniques. Recent evidence supports the superiority of ambulatory or 24-hour blood pressure measurements, rather than office blood pressure measurements, for the assessment of cardiovascular risk. The use of fixed-dose combinations and polypills has been demonstrated to be valid and to provide clinical benefits beyond blood pressure control. There have also been advances in new approaches such as telemedicine, devices and the use of algorithms. Clinical trials have provided valuable data on blood pressure control in primary prevention, during pregnancy and in the elderly. The role of renal denervation remains unsolved but innovative techniques using ultrasound or alcohol injections are being explored. Current evidence and results of latest trials are summarised in this review.