Additional Cardiovascular Risk Research Articles

Cardiovascular Events Risk Factors in Patients with Rheumatoid Arthritis

The objective: is to assess cardiovascular risk and fatal cardiovascular events with consideration of classical and additional cardiovascular risk factors in patients with rheumatoid arthritis.Materials and methods. 56 patients with rheumatoid arthritis aged 48,7±9,52 years were examined. The average disease duration was 9,8±2,7 years. In all patients, classical risk factors of cardiovascular diseases development were determined. 10-year coronary risk according to theFramingham scale and a 10-year fatal risk according to the SCORE scale were calculated for all patients. As additional cardiovascular risk factors markers of systemic inflammation, parameters of the hemostasis system, markers of endothelial dysfunction and damage were studied.Results. At screening for classic cardiovascular factors, the 10-year coronary risk according to the Framingham scale in patients with rheumatoid arthritis was 4,0 %, which was significantly lower than the corresponding risk for a population of a comparable gender and age without rheumatoid arthritis. The 10-year risk of fatal cardiovascular events according to the SCORE scale in the examined patients was 1,0 %, which can be considered as low level of risk. Analysis of additional cardiovascular risk factors allowed to reveal an increase in the C-reactive protein and fibrinogen levels, and a decrease of APTT one. Correlations were revealed between the activity of system inflammation and changes in the hemostasis system (platelet count, APTT, fibrinogen level). Patients with RA showed signs of endothelial damage and its dysfunction, which were significantly correlated with parameterd of system inflammation.Conclusion. The risk of cardiovascular pathology development and fatal cardiovascular events in patients with rheumatoid arthritis, calculated only with classical risk factors scales, is close to the general population one. An analysis of additional risk factors indicates that patients with rheumatoid arthritis show signs of endothelial damage and dysfunction, as well as increased prothrombogenic potential, which are directly related to the activity of systemic inflammation and contribute to the development of high cardiovascular risk in rheumatoid arthritis.

Biochemical and Paraclinical Evaluation of Organ Damage in Arterial Hypertension with Associated Chronic Kidney Disease

Organ damages, which contribute to the overall cardiovascular risk of hypertensive patients, should be early detected, prevented and treated. The study evaluated organ damage in a hypertensive study group with chronic kidney disease (CKD), compared with a study group of hypertension without CKD. Albuminuria was present in 41.2% and reduced estimated glomerular filtration rate [60 ml/min/m2 was present in 72.5% of hypertensive with CKD. The comparison of organ damage revealed in the CKD group a statistical significant higher prevalence of organ damage as follows: intima-media thickness ]0.9 mm in 39.9% vs 10.5%, carotid plaques in 28.2% vs 12.6%, left ventricular hypertrophy in 39.9% vs 31%, ankle brachial index in 6.2% vs 3.5%. Early detection and treatment of additional cardiovascular risk factors as dyslipidaemia and hyperglycaemia, that have significant role in the pathogenesis of organ damage, contribute to the better prevention of cardiovascular and renal complications in hypertension with CKD.

Effect of dulaglutide on cognitive impairment in type 2 diabetes: an exploratory analysis of the REWIND trial

Diabetes is an independent risk factor for cognitive impairment. We aimed to investigate the association between the glucagon-like peptide-1 (GLP-1) receptor agonist dulaglutide and cognitive impairment as an exploratory analysis within the Researching Cardiovascular Events With a Weekly Incretin in Diabetes (REWIND) trial. REWIND is a randomised, double-blind placebo-controlled trial at 371 sites in 24 countries. We included men and women (aged ≥50 years) with either established or newly diagnosed type 2 diabetes and additional cardiovascular risk factors, glycated haemoglobin of up to 9·5% (80 mmol/mol) on a maximum of two oral glucose-lowering drugs with or without basal insulin, and a body-mass index of at least 23 kg/m2. Participants were randomly assigned (1:1) subcutaneous injections once a week of either dulaglutide (1·5 mg) or an equal volume of matching placebo. Randomisation was done using a computer-generated code with stratification by site. Participants and all study personnel were masked to treatment allocation until the database was locked. Participants were followed up at least every 6 months for the composite primary outcome of stroke, myocardial infarction, or death from cardiovascular or unknown causes. Cognitive function was assessed at baseline and during follow-up using the Montreal Cognitive Assessment (MoCA) and Digit Symbol Substitution Test (DSST). We present here the exploratory primary cognitive outcome, which was the first occurrence of a follow-up score on MoCA or DSST that was 1·5 SDs or more below the baseline mean score in the participant's country. All analyses were done using an intention-to-treat approach. The REWIND trial is registered with ClinicalTrials.gov, NCT01394952. Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were randomly assigned to either dulaglutide (n=4949) or placebo (n=4952). During median follow-up of 5·4 (IQR 5·1-5·9) years, 8828 participants provided a baseline and one or more follow-up MoCA or DSST scores, of whom 4456 were assigned dulaglutide and 4372 were assigned placebo. The cognitive outcome occurred in 4·05 per 100 patient-years in participants assigned dulaglutide and 4·35 per 100 patient-years in people assigned placebo (hazard ratio [HR] 0·93, 95% CI 0·85-1·02; p=0·11). After post-hoc adjustment for individual standardised baseline scores, the hazard of substantive cognitive impairment was reduced by 14% in those assigned dulaglutide (HR 0·86, 95% CI 0·79-0·95; p=0·0018). Long-term treatment with dulaglutide might reduce cognitive impairment in people with type 2 diabetes. Further studies of this drug focused on brain health and cognitive function are clearly indicated. Eli Lilly and Company.

P0278CARDIOVASCULAR RISK FACTORS AND THE LONG TERM OUTCOME OF LUPUS NEPHRITIS

Abstract Background and Aims Systemic Lupus Erythematosus (SLE) is associated with an increased risk of cardiovascular morbidity and cardiovascular mortality. The risk of cardiovascular events is 1.3–2.7 times higher in SLE patients than in the general population, and even higher in patients with lupus nephritis (LN). Traditional risk factors as well as SLE-specific and treatment-related factors all contribute to the increased risk of cardiovascular disease. The primary aim of the present study was to evaluate cardiovascular risk factors, morbidity and mortality in patients with LN. Method This is a retrospective study of patients over the age of 16, with LN proved by kidney biopsy and followed up in our department over a period of 17 years. The diagnosis of lupus was made according to criteria of The American College of Rheumatology revised in 1997. Demographic, clinical and para-clinical data were collected from medical observations. Results We collected 155 women and 19 men with a sex ratio F / H of 8.2. The mean age at the time of the discovery of LN was 32.6 years [15-45 years]. Overall median follow-up time was 81.2 months. Renal symptomatology was dominated by proteinuria noted in all patients with an average proteinuria at 3.3 g / 24h, associated to a nephrotic syndrome in 68% of patients, hematuria was present in 69% of patients and renal failure was present in half of cases with an average serum creatinine of 110 µmol / l. At the time of diagnosis of LN, hypertension was noted in 48.9% of cases, diabetes in 2.8% of cases and obesity in 57.4% of cases with an index average body mass of 28.5 Kg / m2. Smoking was reported in 17.2% of the cases. The average cholesterol level was 5,5±2,1 mmol/l, the average triglycerid level was 2,5±1,1 mmol/. Antiphospholipid syndrome was found in 14.9% of cases. We performed 243 renal biopsies with 174 initial and 69 iterative biopsies. The histological lesions were polymorphic dominated by LN class IV (54.3%), arteriolosclerosis was observed in 47.7% and lesions of thrombotic microangiopathy in 29.8%. Corticosteroid therapy was prescribed in all patients combined with immunosuppressive therapy in 54.6% of cases. The overall survival of the patients at 10 years was 85%. During follow-up, cardiovascular complications found in our series were mainly strokes (6.3%) and coronary insufficiency (5.2%) and transient ischemic attack (6.9%). After a univariate analysis, the additional cardiovascular risk factors identified in our study were antiphospholipid syndrome (p = 0.01), renal failure (p = 0.01), long-term corticosteroid therapy (p = 0.009), the chronicity of the disease (evolution of lupus> 10 years) (p = 0.014), proliferative forms (p=0.001), arteriolosclerosis (p=0.0002) and lesions of thrombotic microangiopathy (p=0.018). Survival in patients without cardiovascular risk factors was better (96% vs 88%). Conclusion In conclusion, in addition to traditional risk factors SLE patients have several disease related risk factors that explain increase cardiovascular disease. A careful control for this risk factors is essential to continuously improve survival in SLE.

P0821OBESITY, FAT TISSUE, CELL MEMBRANE INTEGRITY PARAMETERS AND ARTERIAL STIFFNESS IN RENAL TRANSPLANT RECIPIENTS

Abstract Background and Aims Arterial stiffness, altered body composition (increased body fat mass and decreased soft lean mass) and cell membrane integrity (Phase Angle) are acknowledged risk factors for adverse outcomes after kidney transplantation related to cardiovascular diseases. Phase angle is a linear method of measuring the relationship between electric resistance and reactance. Taking the arc tangent value of the ratio of reactance versus electric resistance provides us with the phase angle value. Lower phase angles appear to be consistent with low reactance and equals either cell death or a breakdown in the selective permeability of the cell membrane. The aim of the study was the assessment of the relationship between arterial stiffness and fat tissue parameters, cell membrane integrity marker in renal transplants recipients (RTRs). Method 344 stable RTRs with the mean age 52.7 years, (62.5% M) transplanted between 1994 and 2018 were randomly enrolled to the study. The following parameters of arterial stiffness were measured: brachial-ankle and carotid-femoral pulse wave velocities (baPWV left and right, cfPWV). The obesity and fat tissue (body mass index (BMI), waist to hip ratio (WHR), body fat mass (BFM), fat free mass (FFM), percent fat of the body (PBF), trunk segmental fat analysis (TSFA) and visceral fat area (VFA)) parameters and cell membrane integrity phase angle (PhA) were assessed with InBody 170. Results The median time of dialysis and after kidney transplantation was 58.5 and 78 months respectively. The obesity according to BMI, WHR and VFA was diagnosed in 49.7%, 45% and 44.5% of patients, respectively. The median value of BFM, FFM, VFA, TSFA, PhA and the mean value of PBF were 19.3kg, 55kg, 93.2cm2, 24.9 kg, 4.9 and 27.3%, respectively. We found significant positive correlations between WHR, VFA and baPWV right, baPWV left and cfPWV. PhA correlated with arterial stiffness in univariate (r=-0.34) and multivariate analysis (R=-0.23), negatively (p<0.05). Conclusion 1. Obesity, visceral fat tissue, cell membrane integrity marker influence on arterial stiffness. 2. The analysis of magnitude of obesity, body fat tissue and cell membrane integrity parameters can be used as an additional cardiovascular risk factor in RTRs. 3. The cell membrane integrity impairment correlated with arterial stiffness.

Fenotipo de Cintura Hipertrigliceridémica en la población con Enfermedad Renal Crónica. Cohorte NEFRONA

Background and objectiveThe hypertriglyceridaemic waist (HTW) phenotype is defined for the general population. Chronic kidney disease (CKD) tends to bring on changes in body composition, is associated with higher comorbidity than the general population and, furthermore, shows reverse epidemiology with related prognostic variables like cholesterol and body mass index. Our objective was to identify cut-off points in the population with CKD and to analyse its relationship with cardiovascular risk (CVR). MethodsWe included 2271 CKD patients from the NEFRONA cohort. Triglyceride and waist cut-off points were selected through quintiles analysis and receiver operating characteristic (ROC) curves evaluation, using the presence of moderate to severe atherosclerosis score (AS 2-3) as outcome variable. Then, we analysed HTW prevalence and its association with other cardiovascular risk factors, and we measured the magnitude of its effect on AS 2-3 and cardiovascular event or death (CVEoD) by multivariate regression analysis. ResultsWe selected the cut-off points: triglyceride concentrations ≥143 mg/dl with waist circumference values>102cm in men and 94cm in women (sensitivity 26%; specificity 87%). Specific HTW prevalence was 22.4%, without significative differences between CKD stages. The multivariate regression analysis shows specific HTW as an independent AS 2-3 (OR 1.61; 95% CI: 1.12-2.32, p=0.011) and CVEoD (HR 3.08; 95% CI: 1.66-5.72, p=0.000) risk factor. An interaction between phosphorus level and specific HTW was identified. ConclusionsAdapting the HTW definition might improve specificity to assess cardiovascular risk in the population with CKD. It identifies an additional CVR in a population in which other screening methods have not proven to be useful, and it is easily clinically accessible. Its interaction with phosphorus levels suggests an association between HTW and bone-mineral metabolism regulation.

Effect of Daily Macadamia Nut Consumption on Anthropometric Indices in Overweight and Obese Men and Women

Abstract Objectives We sought to assess the effect of daily consumption of macadamia nuts as 15% of calories on body weight, BMI, waist circumference, percent body fat and skeletal muscle mass in overweight/obese men and women with elevated cardiometabolic risk. Methods Utilizing a randomized crossover design, we randomized 38 subjects to consume macadamia nuts daily as 15% of calories for 8 weeks (intervention) and their usual diet for 8 weeks (control), with a 2-week washout. Three subjects dropped out early; n = 35 for analysis. Subjects were healthy men and postmenopausal women with a BMI of 25–39, a waist circumference of >101.6 cm for men and >88.9 cm for women, and one additional cardiovascular risk factor (fasting plasma glucose >100 mg/dL, triglycerides ≥150 mg/dl, total cholesterol >200 mg/dL, LDL-C > 100 mg/dL, blood pressure ≥130/85 mmHg or taking anti-hypertensive medication). Macadamia nuts were provided in pre-weighed daily portions as 15% of calories calculated using the Mifflin-St. Jeor equation. Percent body fat and skeletal muscle mass (kg) were determined by bioelectrical impedance analysis. A mixed model analysis was performed with treatment, sequence, phase, and baseline values as fixed-effect terms and subjects as a random-effects term. Results Compared to control, consumption of macadamia nuts led to a mean weight change of –348 g (84.13 vs. 83.78 kg; P = 0.15) a mean BMI change of –0.15 kg/m2 (30.61 vs. 30.47 kg/m2; P = 0.12), and a mean waist circumference change of 0.17 cm (107.41 vs. 107.58 cm; P = 0.61). Percent body fat increased by an average of 0.26% after eating nuts (42.70 vs. 42.96%; P = 0.16). Skeletal muscle mass was slightly but significantly lower after eating nuts with a mean change of –0.237 kg (26.33 vs. 26.09 kg; P = 0.017). Conclusions Daily consumption of high-fat macadamia nuts for eight weeks in overweight and obese individuals did not change anthropometrics including body weight, BMI, waist circumference, and % body fat. Skeletal muscle mass was slightly lowered but likely not clinically relevant. Funding Sources Hort Innovation, Sydney, Australia.

Obesity, Fat Tissue Parameters, and Arterial Stiffness in Renal Transplant Recipients

ObjectiveArterial stiffness and altered body composition (increased body fat mass [BFM] and decreased lean body mass) are acknowledged risk factors for adverse outcomes after kidney transplantation related to cardiovascular diseases. The aim of the study was the assessment of the relationship between arterial stiffness and fat tissue parameters in renal transplants recipients (RTrs). MethodsA group of 344 RTrs with stable disease and a mean age of 52.7 years (62.5% men) who underwent transplantation between 1994 and 2018 were randomly enrolled in the study. The following parameters of arterial stiffness were measured: brachial-ankle and carotid-femoral pulse waves velocities (baPWVs left and right, cfPWVs). The obesity and fat tissue (body mass index [BMI], waist-to-hip ratio [WHR], BFM, fat free mass [FFM], percent body fat [PBF], trunk segmental fat analysis [TSFA], and visceral fat area [VFA]) parameters were assessed with InBody 170. ResultsThe median time of dialysis and after kidney transplantation was 58.5 and 78 months, respectively. Obesity according BMI, WHR, and VFA was diagnosed in 49.7%, 45.0%, and 44.5% of patients, respectively. The median value of BFM, FFM, VFA, and TSFA and the mean value of PBF were 19.3 kg, 55 kg, 93.2 cm2, 24.9 kg, and 27.3%, respectively. We found significant positive correlations among WHR, VFA, baPWV right, baPWV left, and cfPWV. ConclusionsObesity and visceral fat tissue influence on arterial stiffness. The analysis of magnitude of obesity and body fat tissue parameters can be used as an additional cardiovascular risk factor in RTrs.

The effect of smoking on atrial and ventricular functions in healthy subjects: A speckle tracking echocardiography study.

Smoking is a well-known risk factor for coronary artery diseases. It is also associated with nicotine-induced myocardial dysfunction. The aim of this study was to evaluate the right and left atrial and ventricular functions in apparently healthy smokers. We included consecutively 80 healthy smokers (56 males, mean age:35.5 ± 8.4 years) and 70 healthy nonsmokers (44 males, mean age:33.9 ± 9.5 years). None of the subjects had any additional cardiovascular risk factor other than smoking. The right and left atrial and ventricular functions were assessed by both conventional and speckle tracking echocardiography. Although there was no significant difference in left ventricular ejection fraction, the smokers had significantly lower ventricular global longitudinal strain than controls (-19.9 ± 2.0% vs -21.2 ± 1.9%, P < .001 and -18.4 ± 2.1% vs -21.8 ± 2.2%, P < .001, respectively, for the left and right ventricle). Smokers had also lower atrial reservoir and conduit strains: 35.9 ± 11.1% vs 40.2 ± 11.2%, P = .022 and 16.7 ± 6.8% vs 19.4 ± 6.8%, P = .016, respectively, for the left atrium, and 33.0 ± 10.6% vs 37.6 ± 11.2%, P = .011 and 15.2 ± 5.6% vs 18.0 ± 6.3%, P = .004, respectively, for the right atrium). Even in apparently healthy people with no other cardiovascular risk factors, smoking is associated with impaired atrial and ventricular functions.

Abnormal left ventricular global strain during exercise-test in young healthy smokers

Background. It is unknown how much precociously the cigarette smoking (CS) may compromise the integrity of the cardiovascular (CV) system. Myocardial function can be routinely assessed by conventional echocardiography, but abnormalities are only detected when somewhat a remodelling has already occurred. These limitations could be overcome by strain imaging. Methods. We evaluated whether young smokers with normal left ventricular (LV) geometry, wall motion and ejection fraction may present abnormalities in myocardial deformation, both at rest and during physical effort. We selected 50 young smokers with no additional CV risk factors, and 60 non-smokers to undergo a standardized exercise-test. Consistently, we evaluated the CV adaptation to exercise by both conventional echocardiography and speckle-tracking analysis (2D-STE). Results. We found no difference between smokers and controls regarding baseline characteristics; as expected, smokers presented with lower HDL-cholesterol (p < 0.005), and higher fibrinogen, C-reactive protein (CRP), and interleukin-6 (p < 0.001). Conventional echocardiography parameters were not different between groups, while we detected a different behaviour of global longitudinal strain (GLS), global circumferential strain (GCS) and twist by 2D-STE during exercise-test. Indeed, GLS, GCS and twist behaved differently during exercise test in smokers with respect to controls. We found an association between CS, inflammation and LV mechanics changes uncovered by physical effort, and regression analysis confirmed that the intensity of the exposure to cigarette smoking, together with the inflammatory status (CRP, fibrinogen and Il-6) plasma levels, drive this impairment. Conclusions. We confirm strain imaging (2D-STE) as a very useful tool to identify early changes in cardiac mechanics, as adaptation to exercise; our findings may reflect a very precocious functional abnormality in active smokers, likely long before structural damage occurs.

Hypertension in people in middle and late adulthood during sports and physical training

Aim. Comparative analysis of changes in blood pressure (BP) measured before and after the physical exertion in veteran athletes and persons practicing physical training (late and middle adulthood). Material and methods . The 200 competitive athletes and 45 persons practicing physical training, aged 40 to 72 years were questioned in order to identify the main factors of cardiovascular risk. All measurements and results obtained under this research were treated with regard to the diagnosis of hypertension (HTN), prior determined by a physician, and also to the administered therapy. Results . A total of 54,7% of subjects was diagnosed with the HTN, with 32,6% out of them not taking antihypertensives. 53% of athletes and 62.2% persons practicing physical training were diagnosed with the arterial hypertension. Among athletes, the HTN incidence was 53%, among persons practicing physical training — 62,2%. Among athletes, 49% had pre-exercise elevated systolic BP (SBP) and 42,5% had elevated pre-exercise diastolic BP (DBP). While only 17% of persons practicing physical training demonstrated the elevated SBP and only 13,3% of them were recorded with the elevated DBP. One third of athletes without HTN in their everyday activities were diagnosed with the elevated both SBP and DBP during physical exertion. Immediately after the exercise stress, 39% of all the examined athletes were diagnosed with the elevated post-exercise SBP, and 36,2% of them with the elevated post-exercise DBP. Among persons practicing physical training, 33% of subjects were diagnosed with the elevated postexercise SBP, and 24,4% of them with the elevated post-exercise DBP. Conclusion. A major part of the athletes are diagnosed with the elevation in pre- and post-exercise BP. Whereas, persons practicing physical training demonstrate normal average pre- and post-exercise SBP and DBP values in most of the cases. Post-exercise differences in BP values in athletes and persons practicing physical training are almost leveled out. Post-exercise HTN &gt;140/90 mm Hg is detected both in people with HTN receiving antihypertensive therapy, and in people without HTN. Elderly people involved in sports or fitness have significant differences in the response of BP to the exertion. However, in a significant part of this HTN people, BP changes during exercise are in the hypertensive range and can be an additional cardiovascular risk factor.

High Blood Pressure Variability is an Additional Cardiovascular Risk Factor

Blood pressure (BP) is a highly variable physiological indicator. Most people have BP changes within 40-50 mmHg during the day. Various external factors (from the patient’s position during BP measurement to poor adherence to therapy and abuse of short-acting antihypertensive drugs) affect the assessed indicators. Evaluation of the average daily, intra-visit, as well as long-term ("from visit to visit") BP variability is used in clinical practice. In the past twenty years a number of major studies demonstrated that increased BP variability is an independent prognostic factor that increases the risk of cardiovascular complications. The largest meta-analysis of 41 studies showed that an increase in long-term BP variability was associated with 15% and 18% increase in total and cardiovascular mortality, respectively. According to the IDHOCO project, the threshold coefficient of variation for day-today variability is &gt;11.0/12.8. Different groups of antihypertensive drugs have an uneven effect on BP variability. Consistent data from ASCOT-BPLA, X-CELLENT and ACCOMPLISH studies indicate that among the main groups of antihypertensive drugs, calcium antagonists, mainly amlodipine, have the greatest potential for the variability reduction. A decrease in BP variability, as shown in a post-hoc analysis of CAMELOT and PREVENT studies, has a positive effect on the incidence of major adverse cardiac events (MACE). Thus, the BP variability is an important indicator that reflects the prognosis in hypertensive patients. BP variability reduction can be considered as one of the independent goals of therapy. Calcium antagonists can be considered as first-line drugs for patients with high BP variability.

Are adipokines associated with atrial fibrillation in type 2 diabetes?

The potential effect of adipokines on the development of AF is yet to be established. The aim of this study was to investigate the association of baseline serum adipokines with 1) the presence of AF at baseline and 2) future risk of AF development. The current study is a sub-analysis of the prospective, randomised AVOCADO (Aspirin Vs./Or Clopidogrel in Aspirin-resistant Diabetics inflammation Outcomes) trial. The AVOCADO study included patients with type 2 DM burdened with at least two additional cardiovascular risk factors and receiving acetylsalicylic acid. In patients included in the current analysis adipokines and inflammatory biomarker levels were measured. Information on the subsequent AF diagnosis was collected after a median of 5.4 years of follow-up. A total of 273 patients with type 2 DM (median age 68 years; 52% male) were included in the initial analysis comparing patients with and without AF at baseline. Patients with diagnosed AF (12%) had higher levels of serum resistin [8.5 (5.8-10.5) vs. 6.9 (5.6-8.7) ng/mL; p = 0.034], adiponectin [6.9 (5.6-8.7) vs. 2.7 (1.8-4.2) ng/mL; p = 0.032], and N-terminal pro-B-type natriuretic peptide [336 (148-473) vs. 108 [45-217]; p < 0.001) than non-AF patients. There were no significant differences in serum leptin, IL-6, and TNF-alpha concentrations between the two groups. From subjects without known AF at study entry, 19% developed AF at follow-up. In logistic regression analysis, baseline adipokine levels did not predict AF development. In type 2 DM, patients with AF have higher resistin and adiponectin concentrations than patients with no AF. None of the studied adipokines proved a predictor of future AF development.

PK/PD modeling based on NO-ET homeostasis for improving management of sunitinib-induced hypertension in rats

Sunitinib is an oral small molecule multitargeted tyrosine kinase inhibitor, which is currently used to treat severe cancers. Clinical research has shown that patients treated with sunitinib develop hypertension. As soon as sunitinib-induced hypertension appears, it is usual to administer anti-hypertension agent. But this treatment may cause acute blood pressure fluctuation which may lead to additional cardiovascular risk. The aim of this study is to establish a mathematical model for managing sunitinib-induced hypertension and blood pressure fluctuation. A mechanism-based PK/PD model was developed based on animal experiments. Then this model was used to perform simulations, thus to propose an anti-hypertension indication, according to which the anti-hypertension treatment might yield relative low-level AUC and fluctuation of blood pressure. The simulation results suggest that the anti-hypertension agent may yield low-level AUC and fluctuation of blood pressure when relative ET-1 level ranges from −15% to 5% and relative NO level is more than 10% compared to control group. Finally, animal experiments were conducted to verify the simulation results. Macitentan (30 mg/kg) was administered based on the above anti-hypertension indication. Compared with the untreated group, the optimized treatment significantly reduced the AUC of blood pressure; meanwhile the fluctuation of blood pressure in optimized treatment group was 70% less than that in immediate treatment group. This work provides a novel model with potential translational value for managing sunitinib-induced hypertension.

The effect of dulaglutide on stroke: an exploratory analysis of the REWIND trial

Cardiovascular outcome trials have suggested that glucagon-like peptide 1 (GLP-1) receptor agonists might reduce strokes. We analysed the effect of dulaglutide on stroke within the researching cardiovascular events with a weekly incretin in diabetes (REWIND) trial. REWIND was a multicentre, randomised, double-blind, placebo-controlled trial done at 371 sites in 24 countries. Men and women (aged ≥50 years) with established or newly detected type 2 diabetes whose HbA1c was 9·5% or less (with no lower limit) on stable doses of up to two oral glucose-lowering drugs with or without basal insulin therapy were eligible if their body-mass index was at least 23 kg/m2. Participants were randomly assigned (1:1) to weekly subcutaneous injections of either masked dulaglutide 1·5 mg or the same volume of masked placebo (containing the same excipients but without dulaglutide). Randomisation was done by a computer-generated random code with an interactive web response system with stratification by site. Participants, investigators, the trial leadership, and all other personnel were masked to treatment allocation until the trial was completed and the database was locked. During the treatment period, participants in both groups were instructed to inject study drug on the same day at around the same time, each week. Strokes were categorised as fatal or non-fatal, and as either ischaemic, haemorrhagic, or undetermined. Stroke severity was assessed using the modified Rankin scale. Participants were seen at 2 weeks, 3 months, 6 months, and then every 3 months for drug dispensing and every 6 months for detailed assessments, until 1200 confirmed primary outcomes accrued. The primary endpoint was the first occurrence of any component of the composite outcome, which comprised non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular or unknown causes. All analyses were done according to an intention-to-treat strategy that included all randomly assigned participants, irrespective of adherence. The trial is registered with ClinicalTrials.gov, number NCT01394952. Between Aug 18, 2011, and Aug 14, 2013, we screened 12 133 patients, of whom 9901 with type 2 diabetes and additional cardiovascular risk factors were randomly assigned to either dulaglutide (n=4949) or an equal volume of placebo (n=4952). During a median follow-up of 5·4 years, cerebrovascular and other cardiovascular outcomes were ascertained and adjudicated. 158 (3·2%) of 4949 participants assigned to dulaglutide and 205 (4·1%) of 4952 participants assigned to placebo had a stroke during follow-up (hazard ratio [HR] 0·76, 95% CI 0·62-0·94; p=0·010). Dulaglutide reduced ischaemic stroke (0·75, 0·59-0·94, p=0·012) but had no effect on haemorrhagic stroke (1·05, 0·55-1·99; p=0·89). Dulaglutide also reduced the composite of non-fatal stroke or all-cause death (0·88, 0·79-0·98; p=0·017) and disabling stroke (0·74, 0·56-0·99; p=0·042). The degree of disability after stroke did not differ by treatment group. Long-term dulaglutide use might reduce clinically relevant ischaemic stroke in people with type 2 diabetes but does not affect stroke severity. Eli Lilly and Company.

Russian Trial ALGORITHM: Implementation of Combined Antihypertensive and Hypolipidemic Treatment for Clinical Efficacy Achievement in Routine Clinical Practice

Aim. To study the clinical outcomes (achievement of target blood pressure [BP]) and tolerability of antihypertensive and hypolipidemic therapy with fixed combinations of indapamide/perindopril, amlodipine/perindopril, amlodipine/indapamide/perindopril and rosuvastatin in patients with hypertension and high/very high cardiovascular risk in real clinical practice.Material and methods. The study included 16,788 patients from 104 cities of the Russian Federation. The duration of observation was 12 weeks. All patients had three monitoring visits. BP level was measured twice during the visits: the arithmetic mean of the obtained parameters was calculated. The results of the study were analyzed and presented by descriptive statistics.Results. The average age of the patients was 60.6±10.2 years; 42.2% of the patients were men and 57.8% women. Patients who demonstrated systolicdiastolic hypertension (BP&gt;140/90 mm Hg) at the initial visit accounted for 73.9% (n=12,413) of the total number of participants. The average level of systolic BP at the inclusion into the study was 162.94±13.07 mm Hg, the level of diastolic BP was 93.43±8.61 mm Hg. As expected, the Russian population consists of over 90% of patients with very high (57%; n=9,586) and high (35.9%; n=6,022) additional cardiovascular risk. Despite the fact that the overwhelming majority of patients with hypertension had a high and very high additional risk, more than a third of patients received monotherapy to control their BP level (36.8%; n=6,182), while 13.8% of patients (n=2,321) had never received antihypertensive therapy before. According to the results of therapy with combination drugs based on perindopril, 92.7% of patients managed to reach the target BP levels of &lt;140/90 mm Hg. After treatment the average level of systolic BP decreased from 162.94±13.07 mm Hg to 127.80±7.56 mm Hg, and the level of diastolic BP – from 93.43±8.61 mm Hg to 78.54±5.59. Adherence to the treatment in more than 97% of cases was recognized as very high and high. Only 10 adverse events were recorded on a large sample of patients during 12 weeks of treatment.Conclusion. In the Russian population, 73.9% of patients with hypertension and high/very high risk do not achieve the target BP levels. Application of combined therapy based on fixed combinations with perindopril allows achieving effective BP control in 93% of patients with hypertension having high and very high risk during 12 weeks with good tolerability of treatment.

Carotid geometry is an independent predictor of wall thickness \u2013 a 3D cardiovascular magnetic resonance study in patients with high cardiovascular risk

BackgroundThe posterior wall of the proximal internal carotid artery (ICA) is the predilection site for the development of stenosis. To optimally prevent stroke, identification of new risk factors for plaque progression is of high interest. Therefore, we studied the impact of carotid geometry and wall shear stress on cardiovascular magnetic resonance (CMR)-depicted wall thickness in the ICA of patients with high cardiovascular disease risk.MethodsOne hundred twenty-one consecutive patients ≥50 years with hypertension, ≥1 additional cardiovascular risk factor and ICA plaque ≥1.5 mm thickness and < 50% stenosis were prospectively included. High-resolution 3D-multi-contrast (time of flight, T1, T2, proton density) and 4D flow CMR were performed for the assessment of morphological (bifurcation angle, ICA/common carotid artery (CCA) diameter ratio, tortuosity, and wall thickness) and hemodynamic parameters (absolute/systolic wall shear stress (WSS), oscillatory shear index (OSI)) in 242 carotid bifurcations.ResultsWe found lower absolute/systolic WSS, higher OSI and increased wall thickness in the posterior compared to the anterior wall of the ICA bulb (p < 0.001), whereas this correlation disappeared in ≥10% stenosis. Higher carotid tortuosity (regression coefficient = 0.764; p < 0.001) and lower ICA/CCA diameter ratio (regression coefficient = − 0.302; p < 0.001) were independent predictors of increased wall thickness even after adjustment for cardiovascular risk factors. This association was not found for bifurcation angle, WSS or OSI in multivariate regression analysis.ConclusionsHigh carotid tortuosity and low ICA diameter were independent predictors for wall thickness of the ICA bulb in this cross-sectional study, whereas this association was not present for WSS or OSI. Thus, consideration of geometric parameters of the carotid bifurcation could be helpful to identify patients at increased risk of carotid plaque generation. However, this association and the potential benefit of WSS measurement need to be further explored in a longitudinal study.

Acute Coronary Syndrome Registry of High Risk Patients: 30-Day Outcome

The aim of the study is to evaluate important additional cardiovascular (CV) risk factors of major adverse cardiac events (MACE) in patients with acute coronary syndrome (ACS) during the first 30 days after index event. Overall 750 patients with ACS were enrolled in the single center prospective registry from 2012-2015yy. 569 patients received dual antiplatelet therapy and in 425 cases platelet function testing (PFT) were performed. Most of the patients characterized as high risk elderly patients with multiple CV risk factors and high comorbidity index. At 30-day follow-up the mortality rate was 10,1%. Singlevariate analysis showed strong association between MACE and age, atrial fibrillation, stroke, chronic kidney disease, low ejection fraction, type 2 myocardial infarction (T2MI). Multivariate analysis showed that high-on-treatment platelet reactivity (PFT&gt; 45%) with odds ratio 4.418 (p=0.0001), chronic kidney disease (OR 6.538 p=0.001) and T2MI (OR 1.925 p=0.0001) were significantly associated with adverse outcome. ACS registry showed high mortality level in real-life practice compared with randomized clinical trials due to the high prevalence of elderly patients with high comorbidity index. Patients with T2MI have significantly more severe prognosis and chronic kidney disease associated with increased MACE. PFT in this category of patients is reasonable for more accurate risk stratification.

Can donor narratives yield insights? A natural language processing proof of concept to facilitate kidney allocation.

Although expedited placement could ameliorate stagnant kidney utilization, precisely identifying difficult-to-place organs is crucial to mitigate potential harms associated with this policy. Existing algorithms have only leveraged structured data from the Organ Procurement and Transplantation Network (OPTN); however, detailed, free text case information about a donor exists. No known research exists about the utility of these data. We developed a model to predict the probability of delay or discard for adult deceased kidney donors between 2010 and 2018, leveraging donor free text data. The resultant model had a c-statistic of 0.75 compared to 0.80 ( Reduced Probability of Delay or Discard [model], r-PODD) and 0.77 ( Kidney Donor Profile Index, KDPI) on the test dataset. Analysis of the top predictive words suggest both known and potentially novel clinical factors (ie, a known factor such as hypertension vs a novel factor such as stents), and nuanced social factors (intravenous drug use) could negatively affect kidney utilization. These findings suggest that donor narratives have utility; the natural language processing (NLP) model is only moderately correlated with existing indices and provides directional evidence about additional cardiovascular risk factors that may affect kidney utilization. More researchis needed to understand the potential to enhance existing indices of kidney utilization to better enable and mitigate the effects of policy interventions such as expedited placement.

Antiphospholipid syndrome and the risk of myocardial infarction: current evidence and uncertainties.

Antiphospholipid syndrome (APS) encompasses a wide spectrum of disease manifestations that may prevail in the form of venous or arterial thrombosis or lead to pregnancy complications in the presence of persisting antiphospholipid antibodies (aPL). Unlike in the case of congenital thrombophilias, in which venous thromboses are more likely to occur as compared with arterial events, aPL may cause thrombosis in both types of vascular systems. Arterial thrombosis in APS is fairly common and often involve coronary or cerebral arteries leading to myocardial infarction (MI) or stroke. In this review, we summarize the complex pathomechanisms leading to aPL‑associated thrombosis and list challenges during the laboratory detection of these antibodies. Specific features of MI in patients with APS are summarized based on a comprehensive literature search of available case reports. Preventive and treatment strategies are discussed based on the current recommendations and most recent evidence. We conclude that the risk of MI in patients with APS is considerable and MI may be the first manifestation of the disease. MI in APS shows specific clinical features including relatively young age at presentation, no sex dominance, often normal coronaries without the sign of atherosclerosis, high risk of recurrent thrombotic events. Treatment of acute MI in patients with APS is often challenging and adverse events, including stent thrombosis, are more frequent as compared with patients without APS. Preventive strategies in APS should be personalized and include strict management of additional cardiovascular risk factors and long‑term anticoagulation with vitamin K antagonists. Current evidence does not support the use of direct oral anticoagulants in the management of patients with APS with arterial thrombosis due to the high risk of recurrent events.