Cardiovascular Disease Continuum Research Articles

SGLT2 Inhibitors in the Cardiovascular Disease

Sodium glucose cotransporter 2 (SGLT2) inhibitors, initially designed for type 2 diabetes management, have exhibited consistent efficacy across the cardiovascular disease continuum. Their benefits are experienced by patients with cardiovascular risk factors, those with established atherosclerotic cardiovascular disease, and even individuals suffering from heart failure (HF). Notably, SGLT2 inhibitors have demonstrated remarkable effectiveness in preventing and managing HF, positioning them as essential primary therapies for HF patients irrespective of their diabetic status. They have emerged as a uniquely effective treatment for HF with preserved ejection fraction, filling a therapeutic gap that previously existed in this population. These cardiovascular benefits are not limited to diabetic patients, indicating a broader potential for SGLT2 inhibitors in cardiovascular care. Their expanded indications suggest a pivotal role in both the prevention and treatment of cardiovascular disease. However, while clinical outcomes with SGLT2 inhibitors are promising, the precise mechanism underlying their cardiovascular protection remains unclear. Further research is warranted to elucidate these mechanisms, potentially unveiling new therapeutic avenues and facilitating the development of novel drugs.

Gut microbiota at different stages of cardiovascular disease continuum

Aim. To study the relationship of gut microbiota (GM) composition with clinical and paraclinical characteristics of patients with coronary artery disease (CAD) and heart failure with reduced ejection fraction (HFrEF).Material and methods. The study included 64 patients (men, 71,9%) with CAD, 33 (men, 87,9%) with HFrEF and 38 (men, 63,2%) with various cardiovascular risk factors (control group). GM composition was assessed using real-time polymerase chain reaction and next- generation sequencing. To identify correlations of GM composition with clinical and paraclinical characteristics, the Spearman rank correlation coefficient (ρ) was calculated. Generalized linear models (QuasiPoisson, overdispersion) with covariates (age, body mass index) were used to compare groups by phylotype.Results. The relative abundance of Bacillota phylotypes is significantly higher in patients with CAD and HFrEF compared to controls (p<0,001). The Bacillota/Bacteroidota dysbiosis ratio was also significantly higher in patients with CAD and HFrEF than in the control group (p<0,001). According to correlation analysis, the relative representation of methanogenic archaea Methanomassiliicoccaceae, Methanomethylophilaceae (ρ=0,49, p<0,0003) directly correlated with ventricular arrhythmias in patients with HFrEF.Conclusion. Patients with CAD and HFrEF differ significantly from the control group in GM composition at the phylotype level. In the study groups, Bacillota/Bacteroidota dysbiosis ratio was also significantly higher than in the control group. The relative abundance of the archaea Methanomassiliicoccaceae and Methanomethylophilaceae is associated with episodes of ventricular tachycardia/ventricular fibrillation.

Role of β-blockers in the cardiovascular disease continuum: a collaborative Delphi survey-based consensus from Asia-Pacific

Objective This Delphi method of consensus was designed to develop scientific statements for β-blockers in the continuum of cardiovascular diseases with a special focus on the role of bisoprolol. Methods Eleven experienced cardiologists from across the Asia-Pacific countries participated in two rounds of the survey. In the first round, experts were asked to rate agreement/disagreement with 35 statements across seven domains regarding the use of β-blockers for treating hypertension, heart failure, coronary artery diseases, co-morbidities, as well as their safety profile, usage pattern, and pharmacokinetic variability. A consensus for a statement could be reached with >70% agreement. Results Except for seven statements, all attained consensus in the first round. In the second round that was conducted virtually, the experts re-appraised their ratings for the seven statements along with a critical appraisal of two additional statements that were suggested by experts in the preceding round. At the end of the second round, the final version included 36 statements (34 original statements, two statements suggested by experts, and the omission of one statement that did not attain consensus). The final version of statements in the second round was disseminated among experts for their approval followed by manuscript development. Conclusion Attainment of consensus for almost all statements reconfirms the clinical benefits of β-blockers, particularly β1-selective blockers for the entire spectrum of cardiovascular diseases.

RISK OF DEVELOPMENT CARDIOVASCULAR СOMPLICATIONS IN PATIENTS WITH ARTERIAL HYPERTENSION AND METABOLIC SYNDROME

The combination of arterial hypertension and metabolic syndrome leads to an increased risk of development cardiovascular complications. Early detection of asymptomatic target organ damage to determine additional risk is important, because pressure-dependent subclinical damage to several organs reflects progression along the cardiovascular disease continuum. The SCORE scale is based on data from a number of recent European multicenter studies and takes into account all variants of fatal cardiovascular events over a 10-year period. However, the SCORE scale does not take into account the presence of such subclinical risk factors for the development of cardiovascular complications as insulin resistance, endothelial dysfunction, microalbuminuria
 The aim was to assess the ten-years risk of development of cardiovascular complications in hypertensive's with metabolic syndrome, depending on the type of insulinemia, endothelial dysfunction, and the presence of microalbuminuria.
 Materials and methods. Were examined 96 patients (34 men, 62 women) with arterial hypertension and metabolic syndrome, average age (57±9) years. Office blood pressure measurement, the level of total cholesterol in the blood and microalbuminuria in daily urine were determined for all patients. An oral glucose tolerance test was performed with parallel determination of the level of endogenous insulin, endothelin-1, and vasculoendothelial growth factor in blood serum by the immunoenzymatic method. Patients were divided into three groups. Group 1 included 29 patients with normal basal and postprandial levels of endogenous insulin; in the 2nd group – 39 patients with reactive hyperinsulinemia, in the 3rd group – 28 patients with spontaneous hyperinsulinemia. To estimate the total cardiovascular risk, the version of the SCORE scale for countries with high cardiovascular mortality was used. Moderate risk criteria are defined – SCORE index level 1-4%, high risk – 5-9% and very high risk – ≥ 10%.
 Research results. A moderate cardiovascular risk prevailed in almost 52% of patients of group 1 with a normal level of endogenous insulin, high – in 35% of patients group 2 with reactive hyperinsulinemia, very high – in 48% of patients group 2 and 43% of patients of group 3 with spontaneous hyperinsulinemia. The highest levels of systolic and diastolic blood pressure were characteristic of high-risk patients with spontaneous hyperinsulinemia combined with impaired glucose tolerance, with increasing of total cholesterol levels in 1.7 times under obesity, increasing of endothelin levels by 7 times, vasculoendothelial growth factor in 2.7 times and the presence of microalbuminuria in 75% of cases.
 Conclusions. More than half patients with arterial hypertensive and metabolic syndrome have a high and very high cardiovascular risk according to the SCORE scale, which is associated with hyperinsulinemia and insulin resistance, hypercholesterolemia and obesity, microalbuminuria and disorders of endothelial vasoregulation. The risk of cardiovascular complications based on subclinical signs of target organs damage to increases with the severity of insulin resistance and progression of endothelial dysfunction, which creates prerequisites for the development of atherosclerosis.

Implementing Carotid Ultrasonography in Optimizing Primary Cardiovascular Prevention Strategy: Has the Time Come?

The cardiovascular (CV) disease continuum begins from a cluster of CV risk factors, proceeds with the development of asymptomatic atherosclerotic lesions and ends with the occurrence of CV events [...].

Modeling biological age using blood biomarkers and physical measurements in Chinese adults.

This study aimed to: 1) assess the associations of biological age acceleration based on Klemera and Doubal's method (KDM-AA) with long-term risk of all-cause mortality; and 2) compare the association of KDM-AA with all-cause mortality among participants potentially at different stages of the cardiovascular disease (CVD) continuum. The present study was based on a subpopulation of the China Kadoorie Biobank, with baseline survey during 2004-08. A total of 12,377 participants free of ischemic heart disease, stroke, or cancer at baseline were included, in which 8180 participants were identified to develop major coronary event (MCE), ischemic stroke (IS), intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH), and 4197 remained free of these cardiovascular diseases before 1 January 2014. These participants were followed up until 1 Jan 2018. KDM-AA was calculated by regressing biological age measurement, which was constructed based on baseline 16 physical and 9 biochemical markers using Klemera and Doubal's method, on chronological age. We estimated the associations of KDM-AA with the mortality risk using the hazard ratio (HR) and 95% confidence interval (CI) from Cox proportional hazard models. We assessed discrimination performance by Harrell's C-index and net reclassification index (NRI). The participants who developed MCE (mean KDM-AA=0.1 year, standard deviation [SD]=1.6 years) or ICH/SAH (0.3±1.5 years) during subsequent follow-up showed accelerated aging at baseline compared to those of IS (0.0±1.2 years) and control (-0.3±1.3 years) groups. The KDM-AA was positively associated with long-term risk of all-cause mortality (HR=1.20; 95% CI: 1.17, 1.23), and the association was robust for participants potentially at different stages of the CVD continuum. Adding KDM-AA improved mortality prediction compared to the model only with sociodemographic and lifestyle factors in whole participants, with the Harrell's C-index increasing from 0.813 (0.807, 0.819) to 0.821 (0.815, 0.826) (NRI=0.011; 95% CI: 0.003, 0.019). In this middle-aged and elderly Chinese population, the KDM-AA is a promising measurement for biological age, and can capture the difference in cardiovascular health and predict the risk of all-cause mortality over a decade. This work was supported by National Natural Science Foundation of China (82192904, 82192901, 82192900, 81941018). The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z), grants (2016YFC0900500) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 91846303), and Chinese Ministry of Science and Technology (2011BAI09B01).

S-29-3: THE RELATIONSHIP BETWEEN VENTRICULAR-ARTERIAL COUPLING AND AEROBIC CAPACITY ACROSS THE CARDIOVASCULAR DISEASE CONTINUUM: FOCUS ON PROXIMAL AORTIC STIFFNESS

Objective: Ventricular-arterial coupling (VAC) can be evaluated as the ratio between arterial stiffness (pulse wave velocity, PWV) and myocardial deformation (global longitudinal strain, GLS). We evaluated VAC across the cardiovascular disease continuum. Design and method: We introduced a Doppler-derived, single-beat technique to estimate aortic arch PWV (aa-PWV) in addition to tonometry-derived carotid-femoral PWV (cf-PWV). We measured PWVs and 3D-GLS in: We evaluated peak oxygen consumption (VO2) and peripheral extraction (AVO2diff) using combined cardiopulmonary-echocardiography exercise stress. Results: aa-PWV was obtainable in all subjects and significantly lower than cf-PWV in all subgroups (p < 0.01). PWVs were directly related and increased with age (all p < 0.0001). cf-PWV/3D-GLS was similarly compromised in HFrEF (1.08 ± 0.36) and HFpEF (1.05 ± 0.22), while aa-PWV/3D-GLS was more impaired in HFpEF (0.69 ± 0.11) than HFrEF (0.60 ± 0.15; p < 0.01). Stage A-B had values of cf-PWV/3D-GLS and aa-PWV/3D-GLS (0.66 ± 0.25 and 0.47 ± 0.12) higher than controls (0.47 ± 0.10 and 0.40 ± 0.10) but lower than Stage C (all p < 0.01). Peak AVO2diff was inversely related with cf-PWV/3D-GLS and aa-PWV/3D-GLS (all p < 0.01). cf-PWV/3D-GLS and aa-PWV/3D-GLS independently predicted peak VO2 in the overall population (adjusted R2 = 0.32 and 0.35; all p < 0.0001) but only aa-PWV/3D-GLS was independently associated with flow reserve during exercise (R2 = 0.51; p < 0.0001). Conclusion: Abnormal VAC is directly correlated with greater severity of HF and worse functional capacity. HFpEF shows a worse VAC than HFrEF when expressed by aa-PWV/3D-GLS.

Cardioprotective effect of thiotriazoline in cancer patients

Aim. To evaluate the effectiveness of morpholinium-methyl-triazolyl-thioacetate (thiotriazoline) as a cardioprotector in patients with non-Hodgkin’s lymphomas who received chemotherapy with the inclusion of anthracyclines.Material and methods. Fifty patients with non-Hodgkin’s lymphomas were examined on the background of antitumor therapy. The patients were divided into 2 following groups: group 1 (n=27) — standard chemotherapy; group 2 (n=23) — thiotriazoline as a cardioprotector. The quality of life was assessed using the SF-36 questionnaire; the level of troponin I and the natriuretic peptide NT-proBNP was determined; an electrocardiography and echocardiography were performed.Results. In the course of the study, significant differences (p<0,05) were found in following parameters: the severity of dyspnea and lower limb edema, alanine aminotransferase, aspartate aminotransferase, creatine phosphokinase, troponin I level, NT-proBNP, corrected QT interval, end systolic volume, left ventricular ejection fraction, E/A ratio. The results obtained indicate the clinical and paraclinical advantage of thiotriazoline and reflect its cardioprotective effect. Conclusion. The use of thiotriazoline makes it possible to prevent and slow down the cardiovascular disease continuum, leading to the development of heart failure or decompensation that exists in this category of patients. Keywords: cardio-oncology, thiotriazoline, heart failure, anthracyclines, cardiotoxicity>˂0,05) were found in following parameters: the severity of dyspnea and lower limb edema, alanine aminotransferase, aspartate aminotransferase, creatine phosphokinase, troponin I level, NT-proBNP, corrected QT interval, end systolic volume, left ventricular ejection fraction, E/A ratio. The results obtained indicate the clinical and paraclinical advantage of thiotriazoline and reflect its cardioprotective effect.Conclusion. The use of thiotriazoline makes it possible to prevent and slow down the cardiovascular disease continuum, leading to the development of heart failure or decompensation that exists in this category of patients.

What is a risk heart rate at various stages of the cardiovascular continuum?

Prevention, detection, and treatment of high blood pressure remain an important public health challenge. There is convincing evidence that heart rate is an important risk factor for cardiovascular disease. Recommendations for the resting heart rate measurement are roughly the same as those used for blood pressure measurement which is usually made during the same session. Across different parts of the cardiovascular disease continuum, different heart rate thresholds are identified. Elevated heart rate identifies patients with hypertension at high cardiovascular risk. One of the important causes of inadequate blood pressure control and at the same time heart rate control is the poor adherence of patients to treatment. It is necessary to individualize the treatment of patients with elevated heart rates throughout the cardiovascular continuum. Fixed-dose combination decreases the risk of medication non-compliance and should be considered in patients with chronic conditions like hypertension for improving medication compliance which can translate into better clinical outcomes.

Cardiac psychology training in a rural health care setting: East Carolina Heart Institute.

The full partnership of clinical health psychology and cardiology optimizes patient-centered care to address the mental and behavioral needs of patients living with heart disease. This scenario is realized as the East Carolina Heart Institute (ECHI) at East Carolina University (ECU) in Greenville, North Caroline with co-location and co-training of psychologists and cardiologists. ECHI provides services to patients across the full disease continuum of cardiovascular disease (CVD), given the higher rates of heart disease in this rural area. The purpose of this article is to describe the cardiovascular behavioral medicine training model for clinical health psychology doctoral students and its adaptation during the coronavirus disease 2019 (COVID-19) era. Through illustrative case examples, we describe the training model before the COVID-19 pandemic, during the transition to telehealth following the onset of the COVID-19 pandemic, and then the entirely telehealth-based service model. We highlight notable strengths and challenges to delivering telehealth care to cardiac patients in a rural setting, while also discussing the health disparities that uniquely occur within this patient population in Eastern North Carolina. This innovative partnership fosters a responsive environment for training and clinical care, where the complex needs of patients with CVD are treated to increase their overall quality of life and well-being. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Health Disparities Across the Continuum of ASCVD Risk.

Despite marked progress in cardiovascular disease management in the last several decades, there remain significant, persistent disparities in cardiovascular health in historically marginalized racial and ethnic groups. Here, we outline current state of health disparities in cardiovascular disease, discuss the interplay between social determinants of health, structural racism, and cardiovascular outcomes, and highlight strategies to address these issues. Across the continuum of atherosclerotic cardiovascular disease (ASCVD) prevention, there remain significant disparities in outcomes including morbidity and mortality by race, ethnicity, and socioeconomic status (SES). These disparities begin early in childhood (primordial prevention) and continue with a higher prevalence of cardiovascular risk factors (primary prevention), and in the uptake of evidence-based therapies (secondary prevention). These disparities are driven by social determinants of health and structural racism that disproportionately disadvantage historically marginalized populations. Structural racism and social determinants of health contribute to significant disparities in cardiovascular morbidity and mortality.

Angiotensin receptor-neprilysin inhibitors for hypertension-hemodynamic effects and relevance to hypertensive heart disease.

Angiotensin receptor-neprilysin inhibitors have multiple beneficial effects on the cardiovascular system. The angiotensin receptor-neprilysin inhibitor sacubitril/valsartan has been shown to effectively reduce ambulatory 24-h blood pressure in patients with hypertension, and improvements in many aspects of hemodynamic function have also been reported. Overall hemodynamic effects on arterial stiffness and nocturnal blood pressure play an important role in the pathogenesis of hypertensive heart disease. Therefore, these could represent mechanistic targets underlying the effects of angiotensin receptor-neprilysin inhibitors on the continuum of cardiovascular disease from hypertension to heart failure. Other potential mechanisms include reductions in circulating volume and sympathetic activity, both of which contribute to the protection against target organ damage and positive changes in cardiac biomarkers seen during angiotensin receptor-neprilysin inhibitor therapy. The mechanisms of action and beneficial effects of angiotensin receptor-neprilysin inhibitors are complementary to those of a number of other treatment options for hypertension, suggesting the possibility of additive or even synergistic benefits. Based on available data, there are a number of patient groups who will benefit from antihypertensive treatment with an angiotensin receptor-neprilysin inhibitor, including those with salt-sensitive hypertension, structural hypertension, resistant hypertension, and hypertension in the presence of heart failure. Overall, angiotensin receptor-neprilysin inhibitors regulate blood pressure and pulse pressure via multiple mechanisms and provide cardiovascular protection. This provides an option for effective intervention early in the vicious cycle of elevated blood pressure and central pressures with progression toward heart failure that should help to address the growing worldwide heart failure epidemic.

Low-dose aspirin for the prevention of atherothrombosis across the cardiovascular risk continuum

Abstract At the 2021 International Aspirin Foundation Symposium of Oriental Congress of Cardiology, a panel of distinguished cardiologists from around the world gathered to present their recent research findings and discuss viewpoints of aspirin use along the entire continuum of cardiovascular disease (CVD) prevention in the general population as well as in specific patient groups. Aspirin produces long-lasting effects on platelet function and cumulative inhibition of platelet thromboxane production by irreversibly inactivating the prostaglandin H-synthase (PGHS). Consistent with saturability of platelet cyclooxygenase 1 (COX-1) inactivation and thromboxane A2 (TXA2) suppression at low doses, a body of convincing evidence showed no additional benefit from high versus low-dose aspirin. Trials of aspirin as primary prevention trials are challenging due to the low event rate and reduced patient compliance over time. Nevertheless, evidence from the ASCEND and TIPS3 trials supported the benefit of aspirin in primary cardiovascular prevention. The Chinese population has among the highest CVD risk in the world. Significant achievement has been made in this respect. For example, the benefit of aspirin use as primary prevention is now recognized in the Chinese guidelines similar to the US, European guidelines, with some unique features that are helpful for the Chinese population (eg, greater emphasis on dynamical reassessment of risk versus benefit). As secondary prevention in patients with transient ischaemic attack (TIA) and minor stroke, low-dose aspirin reduces the risk of major recurrent stroke as well as stroke severity. Peripheral arterial disease (PAD) management and screening is of growing importance. The COMPASS and VOYAGER studies provide new evidence for dual-pathway inhibition (DPI) antithrombotic therapy with low-dose aspirin and reduced-dose rivaroxaban. A major concern with the use of aspirin is the risk of gastrointestinal (GI) bleeding. Strategies to protect patients include eradication of Helicobacter pylori infection and co-prescription of proton pump inhibitors. Different P2Y12 inhibitors and low-dose aspirin have similar levels of bleeding risk, but the risk is magnified when these agents are taken together.

Orthostatic Hypotension: Management of a Complex, But Common, Medical Problem.

Orthostatic hypotension (OH), a common, often overlooked, disorder with many causes, is associated with debilitating symptoms, falls, syncope, cognitive impairment, and risk of death. Chronic OH, a cardinal sign of autonomic dysfunction, increases with advancing age and is commonly associated with neurodegenerative and autoimmune diseases, diabetes, hypertension, heart failure, and kidney failure. Management typically involves a multidisciplinary, patient-centered, approach to arrive at an appropriate underlying diagnosis that is causing OH, treating accompanying conditions, and providing individually tailored pharmacological and nonpharmacological treatment. We propose a novel streamlined pathophysiological classification of OH; review the relationship between the cardiovascular disease continuum and OH; discuss OH-mediated end-organ damage; provide diagnostic and therapeutic algorithms to guide clinical decision making and patient care; identify current gaps in knowledge and try to define future research directions. Using a case-based learning approach, specific clinical scenarios are presented highlighting various presentations of OH to provide a practical guide to evaluate and manage patients who have OH.

Elevated heart rate across cardiovascular continuum and its management

Elevated heart rate in both healthy individuals and patients with coronary artery disease (CAD), acute myocardial infarction (AMI) and heart failure poses a major risk factor for morbidity and mortality. This fact has further been supported by several studies pointing out to elevated resting heart rate as an important marker for this catastrophe necessitating a prompt therapeutic action plan, consisting of early detection and treatment of the risk factors, to achieve ideal heart rates (approximately 60 beats/minute) in patients which could stop or prevent the progression of the cardiovascular disease (CVD) continuum. Lowering heart rate by therapeutic interventions has shown favorable results, but most of the data so far is retrospective and limited to AMI and heart failure with beta-blocker treatment. Addition of newer drugs into the cardiac armamentarium, like ivabradine, a sinus node inhibitor acting by selective heart rate reduction, has shown several beneficial effects in a variety of conditions spanning from stable angina to heart failure. A consensus meeting was held at the national level wherein experts from various parts of the country discussed and reviewed the importance of heart rate lowering across CV continuum and addition of ivabradine for patients with chronic heart failure and chronic stable angina.

Insulin resistance-related differences in the relationship between left ventricular hypertrophy and cardiorespiratory fitness in asymptomatic newly diagnosed hypertensive Black sub-Saharan Africans

Abstract Background Left ventricular hypertrophy (LVH) is associated with impaired cardiorespiratory fitness (CRF), a surrogate marker of poor outcome. Insulin resistance (IR) plays a central role in all stages of cardiovascular disease continuum. Purpose This study evaluates IR-related differences in the relationship between left ventricular mass (LVM) and CRF in asymptomatic newly diagnosed hypertensive patients. Methods In this cross-sectional observational study, 126 asymptomatic newly diagnosed hypertensive participants (50.5±9.5 years) underwent comprehensive resting transthoracic echocardiographic examination and maximal incremental cardiopulmonary exercise test (CPET). CRF was estimated in peak oxygen uptake (VO2 peak). CPET results were compared between participants with and without LVH. Multivariate analysis examined the influence of IR on the observed differences. Results Those with LVH had lower VO2 peak (15.7±5.5 mL min–1 kg–1 vs. 18.4±3.7 mL min–1 kg–1; p=0.001) than those without LVH. In patients with IR, LVM (r=−0.261, p=0.012), LVM indexed to body surface area (LVMIbsa; r=−0.229, p=0.027), and LVM indexed to height to an allometric power of 2.7 (LVMIh2.7; r=−0.351, p=0.001), and VO2 peak were negatively correlated. In hypertensive patients without IR, these same parameters and VO2 peak have no significant correlation. Body mass index (BMI), LVM, and LVMIbsa emerged as independent determinants of VO2 peak, explaining 46.9% of its variability (overall p=0.001) in IR participants, a relationship not found in participants without IR. Conclusions IR may participate in the deterioration of CRF associated with LVH. Targeting IR in hypertensive patients with LVH could improve prognosis. Funding Acknowledgement Type of funding sources: None.

Performances on the Montreal Cognitive Assessment Along the Cardiovascular Disease Continuum.

This study compared performances of different cardiovascular disease profiles on the MoCA and its subscores. Eighty participants (>50years) from two studies conducted at the Montreal Heart Institute were separated into four groups: low cardiovascular risk factors (<2), high cardiovascular risk factors (>2), coronary heart disease, and stable heart failure. ANCOVAs were performed on the total score and on subscores, with sex, age, and education as covariates. Group differences were observed on the MoCA total score (heart failure < low cardiovascular risk), verbal fluency (heart failure < low cardiovascular risk), memory (coronary heart disease < low cardiovascular risk), and orientation (coronary heart disease < low and high cardiovascular risk) subscores. Results suggest that the MoCA, particularly verbal fluency and memory subscores, can detect cognitive changes in later stages of the cardiovascular disease continuum, such as heart failure. Detecting cognitive changes earlier on the cardiovascular disease continuum may require more in depth neuropsychological assessments.

Epidemiology, Pathophysiology, Diagnosis and Treatment of Heart Failure in Diabetes

The cardiovascular disease continuum begins with risk factors such as diabetes mellitus (DM), progresses to vasculopathy and myocardial dysfunction, and finally ends with cardiovascular death. Diabetes is associated with a 2- to 4-fold increased risk for heart failure (HF). Moreover, HF patients with DM have a worse prognosis than those without DM. Diabetes can cause myocardial ischemia via micro- and macrovasculopathy and can directly exert deleterious effects on the myocardium. Hyperglycemia, hyperinsulinemia, and insulin resistance can cause alterations in vascular homeostasis. Then, reduced nitric oxide and increased reactive oxygen species levels favor inflammation leading to atherothrombotic progression and myocardial dysfunction. The classification, diagnosis, and treatment of HF for a patient with and without DM remain the same. Until now, drugs targeting neurohumoral and metabolic pathways improved mortality and morbidity in HF with reduced ejection fraction (HFrEF). Therefore, all HFrEF patients should receive guideline-directed medical therapy. By contrast, drugs modulating neurohumoral activity did not improve survival in HF with preserved ejection fraction (HFpEF) patients. Trials investigating whether sodium-glucose cotransporter-2 inhibitors are effective in HFpEF are on-going. This review will summarize the epidemiology, pathophysiology, and treatment of HF in diabetes.

Modulation of insulin resistance by renin angiotensin system inhibitors: implications for cardiovascular prevention.

Insulin resistance (IR) and the related hyperinsulinamia play a key role in the genesis and progression of the continuum of cardiovascular (CV) disease. Thus, it is reasonable to pursue in primary and secondary CV prevention, the pharmacological strategies that are capable to interfere with the development of IR. The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathogenesis of IR. In particular, angiotensin II (Ang II) through the generation of reactive oxygen species, induces a low grade of inflammation, which impairs the insulin signal transduction. The angiotensin converting enzyme (ACE) inhibitors are effective not only as blood pressure-lowering agents, but also as modulators of metabolic abnormalities. Indeed, experimental evidence indicates that in animal models of IR, ACE inhibitors are capable to ameliorate the insulin sensitivity. The Ang II receptor blockers (ARBs) modulate the peroxisome proliferator-activated receptor (PPAR)-γ activity. PPARâ€"γ is a transcription factor that controls the gene expression of several key enzymes of glucose metabolism. A further mechanism that accounts for the favorable metabolic properties of ARBs is the capability to modulate the hypothalamicâ€"pituitary-adrenal (HPA) axis. The available clinical evidence is consistent with the concept that both ACE inhibitors and ARBs are able to interfere with the development of IR and its consequences like type 2 diabetes. In addition, pharmacological inhibition of the RAAS has favourable effects on dyslipidaemias, metabolic syndrome and obesity. Therefore, the pharmacological antagonism of the RAAS, nowadays, represents the first choice in the prevention of cardio-metabolic diseases.

Type 2 Diabetes Mellitus and Chronic Heart Failure with Midrange and Preserved Ejection Fraction: A Focus on Serum Biomarkers of Fibrosis.

As myocardial fibrosis might be an important contributor to the association of diabetes mellitus with left ventricular (LV) dysfunction and chronic heart failure (HF), we investigated the profile of some proinflammatory, profibrotic biomarkers in patients with type 2 diabetes mellitus (T2DM) at various stages of the cardiovascular disease continuum from absence of clinic since and symptoms to HF with preserved (HFpEF) and midrange ejection fraction (HFmrEF). Material and Methods. Sixty-two patients with T2DM (age 60 [55; 61]), 20 patients without clinical manifestations of HF and 2 groups with clinical manifestations of stable HF, 29 patients with HFpEF, and 13 patients with HFmrEF, were included in the study. The control group consisted of 13 healthy subjects and normal BMI. All patients underwent transthoracic echocardiography, laboratory assessment of N-terminal fragment of the brain natriuretic peptide (Nt-proBNP), highly sensitive C-reactive protein (hsCRP), soluble suppression of tumorigenesis-2 (sST2), galectin-3, C-terminal propeptide of procollagen type I (PICP), N-terminal propeptide of procollagen type III (PIIINP), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of matrix proteinase-1 (TIMP-1). Results. Patients with HFmrEF had higher values of LV volumetric parameters, indexed parameters of LV myocardial mass (LVMM), and higher concentrations of Nt-proBNP (all p < 0.05). The concentrations of galectin-3 were greater in patients with HFpEF and HFmrEF compared to patients without HF (p = 0.01 and p = 0.03, respectively). PICP and PICP/PIIINP ratio were greater in patients with HFmrEF compared to patients with HFpEF (p = 0.043 and p = 0.033, respectively). In patients with T2DM and HF, a relationship was found between galectin-3 and LVMM/body surface area (r = −0.58, p = 0.001), PIIINP, TIMP-1, and LV end-diastolic volume (r = −0.68 and p = 0.042 and r = 0.38 and p = 0.02, respectively). Conclusion. The dynamics at various stages of the cardiovascular disease continuum in the serum fibrosis markers may reflect an increase in fibrotic and decrease in antifibrotic processes already at the preclinical stage of HF. At the same time, the changes found in the circulating procollagen levels may indicate a shift in balance towards type I collagen synthesis in HFmrEF compared with HFpEF.