Increase In Cardiovascular Events Research Articles

Cardiovascular Disease Risk in Living Kidney Donors: Knowns and Unknowns

This review aimed to summarize evidence regarding mid- and long-term cardiovascular risks associated with living kidney donation in adults. Chronic kidney disease is a major risk factor for cardiovascular disease. It is known that glomerular filtration rate declines among many donors after donation; as a result, these donors can be classified as having early stage chronic kidney disease. Even though initial reports suggested no increase in adverse cardiovascular effects compared with control populations, recent data have shown a possible late increase in cardiovascular event rates and small structural and functional cardiovascular abnormalities. The long-term significance of these abnormalities is unknown. It is not possible to draw strong conclusions on whether the reduction in glomerular filtration rate caused by kidney donation causes an increase in adverse cardiovascular events. Further prospective studies are needed to evaluate the natural history of cardiac and vascular structural and functional abnormalities and their clinical significance.

P654 Prognostic evaluation of simplified echocardiographic parameters in acute myocardial infarction

Abstract Introduction In an era where prognostic evaluation is increasingly being improved by echocardiography in acute myocardial infarction (MI), there are also classic 2D echocardiographic parameters that may have potential and practical utility in this area. The aim of this study was to evaluate the prognostic impact of left ventricular end-diastolic diameter (LVEDD), indexed left atrium volume (VOL) and indexed left ventricular mass (LVM) in ST-segment elevation myocardial infarction (STEMI) patients. Methods Retrospective study of consecutive patients with nonfatal STEMI who underwent percutaneous coronary intervention between January/2015 and December/2017. VOL was calculated by the "Area-Length" and LVM by "Cube formula", both indexed to the body surface area. High parameters were considered when: LVEDD >58mm in man or >52mm in woman; VOL >34mL/m2; LVM >115g/m2 in man or >95g/m2 in woman. At a median follow-up of 46 months (IQR 38-58), the endpoints evaluated were acute myocardial infarction (AMI), decompensated heart failure (DHF), and overall mortality. The analysis of events was adjusted for possible confounding factors. Results A total of 200 patients were identified, 72% of whom were men and the mean age was 63.7 ± 13.0 years. There was an increase of the LVEDD in 17.5%, VOL in 42% and LVM in 16.5%. In the multivariate analysis, LVEDD was able to predict significant DHF (HR 2.4, 95% CI 1.2-4.9) and AMI (HR 6.4, CI 95% 1.6-26.0) and VOL only AMI (HR 6.1, 95% CI 1.2-30.1), but not DHF (HR 1.3, 95% CI 0.7-2.6). The presence of increased LVM was not associated with more events of DHF (HR 1.4, IC95% 0.7-3.0) or AMI (HR 3.7, 95% CI 0.9-14.5). None of these parameters reached statistical significance for mortality (LVEDD: HR 1.0, 95% CI 0.3-3.0, VOL: HR 1.9, 95% CI 0.8-4.4, LVM: HR 1.3, 95% CI 0.5-3.5). In the ROC curve analysis, LVEDD showed an area under the curve (AUC) of 0.7 (95% CI 0.6-0.8) for DHF and 0.6 (95% CI 0.5-0.8) for AMI, whereas VOL demonstrated an AUC of 0.7 (95% CI 0.5-0.9) for AMI. CONCLUSION In patients with nonfatal STEMI who underwent percutaneous coronary intervention, LVEDD and VOL are echocardiographic parameters that may still play some role in prognostic evaluation. The presence of elevated LVM was not associated with a significant increase in cardiovascular events.

Impact of Changes to National Hypertension Guidelines on Hypertension Management and Outcomes in the United Kingdom.

In recent years, national and international guidelines have recommended the use of out-of-office blood pressure monitoring for diagnosing hypertension. Despite evidence of cost-effectiveness, critics expressed concerns this would increase cardiovascular morbidity. We assessed the impact of these changes on the incidence of hypertension, out-of-office monitoring and cardiovascular morbidity using routine clinical data from English general practices, linked to inpatient hospital, mortality, and socio-economic status data. We studied 3 937 191 adults with median follow-up of 4.2 years (49% men, mean age=39.7 years) between April 1, 2006 and March 31, 2017. Interrupted time series analysis was used to examine the impact of changes to English hypertension guidelines in 2011 on incidence of hypertension (primary outcome). Secondary outcomes included rate of out-of-office monitoring and cardiovascular events. Across the study period, incidence of hypertension fell from 2.1 to 1.4 per 100 person-years. The change in guidance in 2011 was not associated with an immediate change in incidence (change in rate=0.01 [95% CI, -0.18-0.20]) but did result in a leveling out of the downward trend (change in yearly trend =0.09 [95% CI, 0.04-0.15]). Ambulatory monitoring increased significantly in 2011/2012 (change in rate =0.52 [95% CI, 0.43-0.60]). The rate of cardiovascular events remained unchanged (change in rate =-0.02 [95% CI, -0.05-0.02]). In summary, changes to hypertension guidelines in 2011 were associated with a stabilisation in incidence and no increase in cardiovascular events. Guidelines should continue to recommend out-of-office monitoring for diagnosis of hypertension.

Cinacalcet-induced hypocalcemia in a cohort of European haemodialysis patients: predictors, therapeutic approaches and outcomes

BackgroundCalcimimetic treatment of secondary hyperparathyroidism in chronic dialysis patients is often followed by hypocalcemia.MethodsWe investigated the frequency, predictors, consequences and therapeutic responses following cinacalcet-induced hypocalcemia in an incident European hemodialysis cohort of 1068 patients with a cinacalcet prescription.ResultsOf 905 normocalcemic patients initiating cinacalcet, 67% developed hypocalcemia within 12 months: 68% mild, 23% moderate, 9% severe. Compared to persistently normocalcemic patients, those with severe hypocalcemia were more often diabetic, overweight, had cardiovascular disease, shorter dialysis vintage, used a catheter dialysis access, had fewer active vitamin-D sterols, and exhibited higher CRP and iPTH and lower calcium levels. Multivariate predictors of hypocalcemia included a catheter for vascular access, low albumin and high iPTH. Generally, no therapeutic intervention to prevent hypocalcemia was taken prior to cinacalcet initiation. After the hypocalcemic event, the most common clinical response was no change of the dialysis or medical regimen. Following the hypocalcemic event, iPTH remained low even in those with severe hypocalcemia. The number of deaths and cardiovascular events did not differ between patients with and without hypocalcemia within six months following cinacalcet initiation.ConclusionTwo-thirds of cinacalcet initiated patients experienced hypocalcaemia with 9% being severe. Hypocalcemia was mostly asymptomatic, transient (with and without targeted intervention to correct it) and not associated with an increase in cardiovascular events or deaths.

A Meta-Analysis of Cardiovascular Events Associated with Intravitreal Anti-VEGF Treatment in Patients with Retinal Vein Occlusion

ABSTRACTPurpose: Retinal vein occlusion is associated with an increased risk of cardiovascular diseases. Anti-vascular endothelial growth factor has been widely used as a treatment option. However, the systemic safety of intravitreal anti-vascular endothelial growth factor for retinal vein occlusion patients is still unclear.Materials and Methods: A meta-analysis was conducted to investigate all randomized controlled trials published up to February 2019 of retinal vein occlusion patients who received intravitreal anti-vascular endothelial growth factor vs. control treatments. Fixed effect models were used and results were reported as odds ratios and 95% confidence intervals.Results: Eight trials that evaluated 2320 patients were retrieved. Anti-vascular endothelial growth factor did not significantly increase the risks of cardiovascular events (odds ratio,1.54; 95% confidence interval, 0.66–3.57), hypertension (odds ratio, 0.92; 95% confidence interval, 0.63–1.33), or heart rate disorders (odds ratio,1.53; 95% confidence interval, 0.37–6.28) when compared with control treatment. Subgroup analyses did not show a significant increase of cardiovascular events in aflibercept (odds ratio,1.96; 95% confidence interval, 0.44–8.81) vs. ranibizumab trials (odds ratio, 1.47; 95% confidence interval, 0.54–4.02); 0.5 mg ranibizumab trials (odds ratio, 1.73; 95% confidence interval, 0.61–4.96) vs. 0.3 mg ranibizumab trials (odds ratio, 0.70; 95% confidence interval, 0.14–3.59); nor branch retinal vein occlusion (odds ratio, 1.32; 95% confidence interval, 0.40–4.33) vs. central retinal vein occlusion trials (odds ratio, 1.93; 95% confidence interval, 0.59–6.29).Conclusions: Intravitreal administration of anti-vascular endothelial growth factor did not significantly increase the risks of cardiovascular events, hypertension or heart rate disorders in retinal vein occlusion patients.

HTA et traitement hormonal de la menopause

Can menopausal hormone therapy (HT) be used in hypertensive women? The group of experts of the French Society of Hypertension has carried out a review of the recent literature in order to answer this question, based on the most recent scientific publications. If use of oral HT is associated with a discreet increase in blood pressure, the transdermal route seems to be safer. The first results of major randomized trials of HT had alerted to an increase in cardiovascular events and breast cancer with the use of oral HT, generally, tipping the benefit-risk balance of the deleterious side. Complementary analyzes have shown the importance of the window of intervention (less than 10 years after the menopause) and the age of the woman to start the HT. On the contrary, they have shown a significant decrease of the coronary events. For woman suffering from hypertension and important climacteric symptoms, it is important to evaluate the whole cardiovascular risk in order to decide the possibility of prescribing a HT. Thus, the group of experts proposes a prescription assistance algorithm based on the stratification of cardiovascular risk, always favoring, when it is authorized, HT by transdermal route of administration.

Association of high density lipoprotein levels with advancing age in type 2 diabetes patients in Tertiary Hospital.

Background: HDL particles have several biological functions. Low levels of HDL-cholesterol are responsible for atherosclerotic disease. Type 2 diabetes is a metabolic disease of chronic etiology and low HDL‐cholesterol is frequent finding in diabetics. Levels of HDL with advancing age are inconsistent, few study show decline in HDL with increasing age while others show vice versa results. Objectives: Objective of this study was to establish an association between low HDL levels with advancing age in type 2 diabetic patients. Study Design: Cross sectional descriptive study. Setting: Diabetes Outpatient Department Nishtar Hospital Multan. Period: 6 months extending from March 2018 to August 2018. Materials and Methods: 145 patients with newly or previously diagnosed type 2 diabetes mellitus, age >35 years were considered for the study. Those diabetics who had family history of dyslipidemias (to rule out familial hyperlipidemias) were excluded. Study was started after acquiring permission from ethical committee. All the patients were evaluated for the HDL levels by getting a fasting lipid assay. Results: Out of 145 cases 78 (53.6%) were males while remaining 67 (46.4%) were female. Mean age of the patients was 57.27 + 6.91 years. Mean HDL level was 37.82 + 8.42. It was seen that HDL is low in 116/145 (80%) patients. Those diabetic patients who were < 60 (91 cases), HDL was noticed to be low in 67/91(73.62%) patients. Among patients >60 years (54 cases), HDL was identified to be low in 49/54(90.7%) patients. P-value was found out to be 0.012 Conclusion: Due to falling levels of HDL with advancing age in diabetic patients, there is increase in cardiovascular events in elderly diabetic patients. So the measures which tend to increase HDL level will also give protection against adverse cardiovascular event in elderly diabetics.

Abstract 498: The Effects of Low-carbohydrate High-fat Diet on Vascular Remodeling

Background: Low carbohydrate diet (LCD) has been reported to reduce body weight and cardiovascular risk factors, including diabetic mellitus and dyslipidemia. Therefore, LCD was once expected to prevent cardiovascular events. However, recent meta-analysis reported that LCD was related to an increase in cardiovascular events. Moreover, other cohort studies reported that higher all-cause and cardiovascular mortality were observed only in LCD with animal derived-fat (LCD-A), not in LCD with plant derived-fat (LCD-P). Precise mechanisms of these effects have not been clarified, so we explored the potential roles of LCD-A and LCD-P in blood vessel remodeling by using two types of vascular disease model mice, atherosclerotic model and vascular injury model. Method: We generated two types of LCDs, beef tallow-based LCD (LCD-A) and cacao butter-based LCD (LCD-P). Six-week-old male ApoE Knockout (ApoE KO) mice (atherosclerosis model mice) and wild-type mice were subjected to LCD-A, LCD-P or normal chow for 14 weeks, and %plaque area of aortic root and serum lipid profile were measured. For vascular injury model, mice were inserted with a wire in a femoral artery of male 10-week-old wild-type mice and subjected to the three-types chow. After 4 weeks, femoral arteries were excised and embedded in paraffin and assessed with the extent of vascular injury severity. The femoral artery without injury on the other side was served as control. Results: In ApoE KO mice, serum levels of total cholesterol (TC) and triglyceride (TG) were decreased in LCD group (TC: p<0.01, TG: p<0.05 vs normal chow), but there was no significant difference between LCD-A to LCD-P. In wild-type mice, serum TC level was increased in LCD-A group (p<0.0001 vs normal chow). LCD had no effect on %plaque area of aortic root in ApoE KO mice. In vascular injury model mice, there was no significant difference in the extent of neointimal hyperplasia induced by wire-injury among groups. Conclusion: Our preliminary data showed that LCD had no effect on vascular remodeling despite the presence of significant alteration in lipid profiles. Additional experiments are needed to confirm the results and clarify the precise mechanisms.

The effects of blood pressure components on cardiovascular events in a Korean hypertensive population according to age and sex: A nationwide population-based cohort study.

There is no known study regarding the usefulness of each blood pressure (BP) component based on stratification by age and sex for predicting cardiovascular (CV) events among hypertensive populations without chronic kidney disease (CKD) or diabetes mellitus (DM). This study was performed to investigate the association of BP components and CV events in a Korean hypertensive population according to age and sex. A total of 22,853 Korean hypertensive participants without CKD and DM were stratified into six groups according to age [40–49, 50–59, and 60 years or older] and sex. In each group, multivariate Cox proportional regression analysis was performed to reveal the associations of BP components [systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP)] with CV events. The increase in PP and decrease in DBP were significantly associated with increase of CV events in males, but neither BP component was significantly associated with risk of CV events in females. When subjects were stratified by age and sex, an increase of SBP or PP was significantly related to the increased risk of CV events in 40's male group, and only the elevation of PP was significantly associated with increase in incidence of CV events in 50's male group, while a decrease in DBP was significantly associated with increased risk of CV events in older male group. In addition, there were no the significant associations with the incidence of CV events in MAP, after stratification according to age and sex. In conclusion, this study suggests that, in hypertensive populations, BP management may need to be performed after full consideration of age and sex.

PS1194 AGE ≥59 YEARS IS ASSOCIATED WITH A HIGHER PROBABILITY OF CARDIOVASCULAR EVENTS IN PATIENTS RECEIVING NILOTINIB FOR CML: A SINGLE CENTRE RETROSPECTIVE ANALYSIS.

Background:In recent years, the use of second‐generation TKIs has increased in both first and second‐line settings in CML. Extended follow‐up of the phase III study of first‐line nilotinib (NIL) (ENESTnd) saw an unexpected increase in cardiovascular events (CVE) in the NIL arms, particularly in patients (pts) with higher Framingham risk scores. However, ‘real‐life’ data on the risk of CVE in Nil treated pts are still limited.Aims:We aimed to determine the probabilities of all CVE and ischaemic arterial events (IAE) at any time from NIL start, in a ‘real‐life’ setting.Methods:We retrospectively analysed 193 CML pts (75 male, 49.2%) given NIL in our centre. Univariate analysis was performed by Kaplan‐Meier and multivariate analysis by Cox proportional hazard model. For both univariate and multivariate analysis, the impact of cardiovascular risk factors (CVRF) was analysed independently of age.Results:The median ages at diagnosis and start of NIL were 46 (18–89) and 51 (20–89), respectively. The overall follow‐up from diagnosis was 110 mths (12–286) and from start of NIL 37 mths (0.1–139). Baseline CVRF were known for 143/193 pts (74%). At least 1 CVRF was present in 94/143 pts (65.7%) and were more common in pts > 60 (p < 0.001). A total of 70 CVE occurred in 50/193 pts (25.9) (Figure 1a). The median duration of NIL therapy in those with CVE was 35.3 months vs 38.5 months in unaffected pts. The median times to occurrence of any CVE or IAE were 19.6 months (0.1–88) and 28.6 months (0.17–85), respectively. The 3 and 5 probabilities of any CVE were 18.1% (95%CI: 17.5–18.7) and 27.9% (95%CI: 27.2–28.6), respectively, while for IAE these were 10% (95%CI: 9.6–10.5) and 13.7% (95%CI: 13.1–14.3), respectively. The duration of NIL doses of 600–800 mg in pts experiencing IAE was 25.8 months (0.17–85), compared to 14.7 months (0.2–124) in unaffected pts (p = 0.86); for CVE, these periods were 24.1 months (0.1–88) and 12.4 months (0.2–124), respectively (p = 0.45). In univariate analysis, age ≥51, presence of any CVRF and male sex were significantly associated with a higher probability of CVE (p = 0.001, p = 0.025, p = 0.005, respectively), while only age ≥51 was significant for the occurrence of IAE (p = 0.0001). ROC analysis of age and occurrence of IAE identified 59 years as the cut‐off with highest sensitivity and specificity (AUC 0.738, p < 0.001). Using this information, the 5 year probability of any CVE was 47.5% (95%CI: 46.1–48.9) for pts ≥59 years and 17.7% (95%CI: 16.9–18.5) for pts <59 years (p = 0.000058), while for IAE this was 27.5% (95%CI: 26.3–28.8) vs 6.4% (95%CI: 5.9–6.9), respectively (p = 0.000028)(Figure 1b). In multivariate analysis, age ≥ 59 and male sex remained significantly associated with occurrence of CVE (HR = 2.2[95%CI: 1.4–4.8], p = 0.001 and HR 1.8 [95%CI: 0.9–3.2], p = 0.047, respectively); age ≥ 59 was again the only variable significantly associated with IAE (HR = 5.23[95%CI: 2.2–12.7], p = 0.0001). At last follow‐up 182 pts (94.3%) are still alive, of whom 82 (47%) remain on NIL, 2 (1%) on imatinib, 33 (18%) on dasatinib, 24 (13%) on bosutinib, 9 (5%) on ponatinib, 1 on ABL001, 31 off‐TKI (20 in TFR and 11 post‐allogeneic transplant). Eleven patients (5.7%) have died, due to CML‐progression (6), secondary malignancy (1), cardiovascular disease (1) and unknown causes after loss to follow‐up (3).Summary/Conclusion:Although requiring validation by larger studies, our data confirm the significant association of NIL with long‐term CVE and identifies age as the most critical factor for their occurrence.image

Long-term safety and tolerability of erenumab: Three-plus year results from a five-year open-label extension study in episodic migraine.

BackgroundPreviously published three-month placebo-controlled and one-year open-label clinical trial data have provided information on the efficacy and safety of erenumab.MethodsInterim analysis was undertaken from an ongoing five-year open-label treatment phase after all patients completed three years in the open-label treatment phase or discontinued the study. Adult patients with episodic migraine enrolled in the open-label treatment phase initially received 70 mg erenumab monthly. A protocol amendment increased the dosage to 140 mg monthly to assess long-term safety of the higher dose. Safety and tolerability were assessed by monitoring adverse events, electrocardiograms, laboratory assessments, and vital signs.ResultsOf 383 patients enrolled in the open-label treatment phase, at data cutoff 235 (61.3%) remained in the study, all received 140 mg for ≥1 year. Median (Q1, Q3) exposure (70 or 140 mg) for all patients enrolled was 3.2 (1.3, 3.4) years. The most frequent adverse events (≥4.0/100 patient-years) were reported as viral upper respiratory tract infection, sinusitis, influenza, and back pain. Exposure-adjusted serious adverse event rates were 4.2/100 patient-years. There was no increase in cardiovascular events over time.ConclusionsIn this long-term study of a CGRP-receptor antibody, erenumab was found to be safe and well-tolerated with a spectrum and rate of adverse events consistent with shorter-term placebo-controlled studies.Trial registrationClinicalTrials.gov NCT01952574

Cardiometabolic Effects of Endocrine Treatment of Estrogen Receptor-Positive Early Breast Cancer.

Estrogen receptor–positive early breast cancer is common and has a relatively good prognosis. It shares risk factors with cardiovascular disease, and cardiovascular disease is an important competing cause of mortality. Adjuvant endocrine therapy with aromatase inhibitors (requiring concomitant ovarian suppression in premenopausal women) or selective estrogen receptor modulators (usually tamoxifen) exert oncologic benefits by respectively inhibiting estradiol synthesis or breast estrogen receptor signaling. Aromatase inhibitors cause systemic estradiol depletion. Tamoxifen has mixed agonistic/antagonistic effects in a tissue-dependent fashion. Given that estrogens modulate cardiometabolic risk, a review of the effects of endocrine therapy on cardiometabolic outcomes is pertinent. The current, but limited, evidence suggests that tamoxifen treatment, although associated with increases in body fat, hepatic steatosis, serum triglycerides, and diabetes risk, modestly reduces low-density lipoprotein cholesterol and lipoprotein(a) and may have favorable effects on markers of subclinical atherosclerosis. Tamoxifen is associated with either no effect on, or a reduction in, cardiovascular events, and it is associated with an increase in venous thromboembolic events. Aromatase inhibitors, although fewer studies are available and often confounded by comparison with tamoxifen, have not been consistently associated with adverse changes in cardiometabolic risk factors or increases in cardiovascular events. Further clinical trials designed to evaluate cardiometabolic outcomes are needed to more accurately determine the effects of endocrine therapy on cardiovascular risks, to inform individualized decisions regarding choice and duration of endocrine therapy, and to implement evidence-based strategies to mitigate cardiometabolic risks. In the meantime, although breast cancer–specific evidence for benefit of lifestyle measures is available and recommended routinely, proactive monitoring and treatment of cardiovascular risk factors should follow general population recommendations.

ВПЛИВ АНТИТРОМБОЦИТАРНОГО ЛІКУВАННЯ НА АГРЕГАЦІЙНУ ЗДАТНІСТЬ ТРОМБОЦИТІВ У ХВОРИХ НА ІШЕМІЧНУ ХВОРОБУ СЕРЦЯ ТА У ПОЄДНАННІ З ЦУКРОВИМ ДІАБЕТОМ 2-ГО ТИПУ

Кількість хворих на цукровий діабет (ЦД) неухильно зростає і таке стрімкезбільшення призводить до зростання кардіоваскулярних подій, здебільшого внаслідок ішемічноїхвороби серця (ІХС), при якій коронарний атеросклероз та його прогресування є однією ізпричин смертності. Перебіг атеросклерозу тісно пов'язаний із станом системи гемостазу.Основу розвитку атеросклерозу складає саме артеріальний тромбоз, при цьому активаціятромбоцитів відіграє провідну роль у порушенні гемостазу при ІХС, підвищуючи ризиктромботичних ускладнень. На сьогодні дані про взаємозв’язок різних ланок гемостазу у хворихна ІХС у поєднанні з ЦД є неоднозначними, ускладнюючи прогнозування несприятливихнаслідків з урахуванням стану тромбоцитарного гемостазу.Враховуючи актуальність теми метою даного дослідження було оцінити спонтанну таіндуковану агрегацію тромбоцитів у пацієнтів з різними формами гострої ІХС (ГІХС) тавиявити особливості агрегаційної активності тромбоцитів при поєднанні ГІХС та ЦД.Адекватне зниження функціональної активності тромбоцитів у пацієнтів із ІХС, якіотримують антитромбоцитарне лікування, є основою ефективної профілактикитромбоутворення в коронарних судинах та розвитку несприятливих серцево-судинних подій.Проте згідно отриманих даних, найбільша активація тромбоцитарного гемостазуспостерігалася у групі хворих із ГІХС у поєднанні з ЦД 2 типу, де відзначалося достовірне(відносно групи контролю) підвищення рівня спонтанної агрегації тромбоцитів у 4,6 разів. Втой час, як відсоток хворих, у яких підвищувались вище зазначені показники був достовірноменшим у групі хворих на ГІХС без порушень вуглеводного обміну. У пацієнтів з ГІХС упоєднанні з ЦД 2 типу спостерігалась також активація швидкості спонтанної агрегації, щона 30 % прискорювало формування агрегатів у порівнянні з групою ізольованої ГІХС (p<0,05).При вивченні індукованої агрегації тромбоцитів враховувалось, що пацієнти обох групотримували подвійну антитромбоцитарну терапію, що мало суттєво позначитись на їхактивності. Проте, очікуване пригнічення агрегаційного потенціалу виявилось лише при діїарахідонової кислоти (АК). Так, ступінь агрегації тромбоцитів у відповідь на АК у групі І був у1,9 рази достовірно нижчим за контрольні значення 18,8% [12,1; 26,4], у групі ІІ – у 1,5 рази істановив 24,38% [21,5; 32,9] (p<0,001 для обох випадків). За даними АДФ-індукованої агрегаціїтромбоцитів вплив антиагрегантних препаратів виявився менш ефективним. Так, помірнезменшення ступеню АДФ-агрегації спостерігалося лише в групі ізольованої ГІХС, показникиякої були в 1,42 рази нижчими, ніж в контролі (р<0,01). Таким чином, проведення подвійноїантитромбоцитарної терапії супроводжувалось ефективним зниженням тромбоцитарнихфункцій лише у групі хворих з ізольованою ГІХС.

Usefulness of antidiabetic alpha-glucosidase inhibitors: a review on the timing of administration and effects on gut hormones.

Elevation of postprandial plasma glucose is correlated with an increase in cardiovascular events, and alpha-glucosidase inhibitors (αGIs) are effective at reducing postprandial glucose levels. In Japan, the αGIs acarbose, voglibose, and miglitol have been available since 1993, 1994, and 2006, respectively. Dipeptidyl peptidase-4 (DPP-4) inhibitors are also effective at reducing postprandial glucose levels, and they have been available in Japan since 2009. A combination therapy of αGI, miglitol, and the DPP-4 inhibitor, sitagliptin, is more effective at decreasing postprandial glucose levels than monotherapy with either miglitol or sitagliptin. Moreover, the combination therapy of miglitol and sitagliptin is more effective at increasing postprandial active glucagon-like peptide-1 (GLP-1) levels than monotherapy. Peptide YY (PYY) has appetite-suppressing and gastric-emptying effects similar to GLP-1. In healthy individuals, miglitol increases the postprandial total PYY; however, combination therapy of miglitol and vildagliptin does not change postprandial total PYY levels. αGIs are typically prescribed to be taken just before a meal, which can result in decreased drug adherence. Different patterns of αGI intake were examined, and the results showed that miglitol or acarbose administration after a meal is effective. The effects of taking miglitol dissolved in water during a meal appeared to be similar to that of taking miglitol as a tablet just before a meal. The long-term effects of taking miglitol dissolved in water should be evaluated in future studies. αGIs may be effective even when they are not taken before a meal, and a more flexible administration may improve drug adherence.

Are All Oral COX-2 Selective Inhibitors the Same? A Consideration of Celecoxib, Etoricoxib, and Diclofenac.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used for the treatment of arthritic conditions. Drugs in this heterogeneous class alleviate pain and inflammation by inhibiting cyclooxygenase-2 (COX-2). Cyclooxygenase-1 (COX-1) inhibition has traditionally been associated with increased gastrointestinal (GI) harm, whereas increased COX-2 selectivity has more recently become associated with greater risk of cardiovascular (CV) harm. When the entirety of data is considered, NSAIDs can be seen to exhibit a range of COX isoform selectivity, with all oral NSAIDs appearing to be associated with an increase in CV events. This review focuses on a comparison of the efficacy and the GI and CV safety profiles of three commonly used NSAIDs—celecoxib, etoricoxib, and diclofenac—using direct comparisons where available. While all three treatments are shown to have comparable efficacy, there are differences in their safety profiles. Both celecoxib and etoricoxib are associated with less GI harm than diclofenac despite the similarity of its COX-2 selectivity to celecoxib. Each of the three medicines under consideration is associated with a similar overall risk of CV events (fatal and nonfatal heart attacks and strokes). However, there are consistent differences in effects on blood pressure (BP), reported both from trials using ambulatory techniques and from meta-analyses of randomized trials, reporting investigator determined effects, with etoricoxib being associated with a greater propensity to destabilize BP control than either diclofenac or celecoxib.

Increased Frequency of In-Center Hemodialysis as Rescue Therapy: Impact on Hospitalization for Acute Cardiovascular Events

Background: The intermittency of conventional hemodialysis (HD) leads to an increase in cardiovascular events. Objective: We aimed to evaluate the effect of in-center frequent HD (FHD, 4–6 times a week) as a rescue option for cardiovascular events. Method: Patients who failed to achieve fluid volume control with conventional HD (thrice a week) were administered FHD. A total of 52 patients were divided into 2 groups by left ventricular ejection fraction (LVEF): low ejection fraction (LEF [n = 26], LVEF < 55%) and normal ejection fraction (NEF [n = 26], LVEF ≥55%). Mortality and hospitalization rates were evaluated. Results: All-cause mortality tended to be higher in the LEF than in the NEF group (p = 0.09). The 1-year hospitalization rate for acute cardiovascular events decreased in both LEF (1.24–0.89; p = 0.049) and NEF (0.36–0.16; p = 0.01) groups. In Cox regression models, LVEF < 55% (hazard ratio 3.81; 95% CI 1.15–12.66; p = 0.03) was identified as the risk factor for hospitalization for acute cardiovascular events. Conclusion: In-center FHD may decrease acute cardiovascular events.

Profound Perturbation of the Metabolome in Obesity Is Associated with Health Risk

SummaryObesity is a heterogeneous phenotype that is crudely measured by body mass index (BMI). There is a need for a more precise yet portable method of phenotyping and categorizing risk in large numbers of people with obesity to advance clinical care and drug development. Here, we used non-targeted metabolomics and whole-genome sequencing to identify metabolic and genetic signatures of obesity. We find that obesity results in profound perturbation of the metabolome; nearly a third of the assayed metabolites associated with changes in BMI. A metabolome signature identifies the healthy obese and lean individuals with abnormal metabolomes—these groups differ in health outcomes and underlying genetic risk. Specifically, an abnormal metabolome associated with a 2- to 5-fold increase in cardiovascular events when comparing individuals who were matched for BMI but had opposing metabolome signatures. Because metabolome profiling identifies clinically meaningful heterogeneity in obesity, this approach could help select patients for clinical trials.

Microparticles harbouring Sonic hedgehog morphogen improve the vasculogenesis capacity of endothelial progenitor cells derived from myocardial infarction patients.

Endothelial progenitor cells (EPC) play a role in endothelium integrity maintenance and regeneration. Decreased numbers of EPC or their impaired function correlates with an increase in cardiovascular events. Thus, EPC are important predictors of cardiovascular mortality and morbidity. Microparticles carrying Sonic hedgehog (Shh) morphogen (MPShh+) trigger pro-angiogenic responses, both in endothelial cells and in ischaemic rodent models. Here, we propose that MPShh+ regulates EPC function, thus enhancing vasculogenesis, and correcting the defects in dysfunctional EPC obtained from acute myocardial infarction (AMI) patients. The mechanisms underlying Shh pathway function and nitric oxide (NO) production in EPC were evaluated. MPShh+ increased both the in vitro and in vivo vasculogenic capacity of EPC isolated from adult human peripheral blood samples. MPShh+ treatment significantly increased the expression of Shh signalling pathway genes (PTCH1, SMO, and GLI1) and masters of pro-angiogenic genes (NOS3, VEGFA, KDR, and KLF2) in EPC. Moreover, MPShh+ increased both the protein expression and activity of eNOS, resulting in increased NO production. Most importantly, MPShh+ improved the vasculogenic capacity of EPC from AMI patients to levels similar to that of EPC from healthy patients. All these effects were due to the activation of Shh pathway. MPShh+ increase both the vasculogenesis of EPC and their capacity to produce NO, including EPC from patients who have recently suffered an AMI. This study emphasizes MPShh+ and EPC as potential therapeutic tools for improving vascular regeneration as a treatment for cardiovascular ischaemic disease.

Sex Differences in the Prognostic Power of Brain Natriuretic Peptide and N-Terminal Pro-Brain Natriuretic Peptide for Cardiovascular Events - The Japan Morning Surge-Home Blood Pressure Study.

Brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are prognostic biomarkers. Although these 2 peptides differ with regard to biological characteristics, there are few reports on the differences between BNP and NT-proBNP with regard to cardiovascular events or according to sex.Methods and Results:Between 2005 and 2012, this study analyzed 3,610 of 4,310 Japanese outpatients (mean age, 65 years; men, n=1,664; women, n=1,947) with a history of at least one cardiovascular event who were recruited to the Japan Morning Surge-Home Blood Pressure Study. During an average 4-year follow-up, there were 129 cardiovascular events. Both median BNP (21.1 pg/mL; IQR, 10.9-40.6 pg/mL vs. 16.2 pg/mL, IQR, 7.2-36.2 pg/mL, P<0.001) and median NT-proBNP (54.7 pg/mL; IQR, 30.2-102.6 pg/mL vs. 44.9 pg/mL, IQR, 20.7-92.6 pg/mL, P<0.001) were significantly higher in women than in men. A 1-SD increment in log-transformed BNP (hazard ratio [HR], 2.18; 95% CI: 1.53-3.10) and NT-proBNP (HR, 2.39; 95% CI: 1.73-3.31) was associated with a significant increase in cardiovascular events in women; in men, only NT-proBNP showed this association. There was an interaction between log-transformed BNP (P=0.007) or NT-proBNP (P=0.001) and cardiovascular events according to sex. Both BNP and NT-proBNP predicted cardiovascular outcomes in a large Japanese clinical population. BNP and NT-proBNP were significantly stronger predictors in women than in men.

Effects of brisk walking on autonomic nervous system reactivation in nursing home residents

The decrease of the autonomic nervous system (ANS) activity that occurs with age is associated with an increase of cardiovascular events and morbidities. It has been shown that physical activity helps reducing the ANS activity age-related decline but remains poorly practiced among nursing home residents. Therefore, we aim to compare the effects of a 9-month brisk walking training (1 time a week or 3 times a week) on the ANS activity in frail nursing home residents. One hundred 60-year-old subjects and older will be recruited within the ten nursing homes of La mutualité française Loire Haute-Loire, France (ClinicalTrials.gov identifier: NCT03302923 ) and will be randomized into 3 groups: G1: one brisk walking session a week; G2: three brisk walking session a week; G3: Control group (no training). Testing procedure will occur at the inclusion and after 3 months, 6 months and 9 months of training. The primary outcome is the heart rate variability measured by 24 hours Holter ECG, especially global and parasympathetic indices such as SDNN and RMSSD respectively. The maximal distance performed during the 6-minute walk test is also used as a secondary outcome measure. Twenty-three subjects aged 80.1 ± 10.7 years currently accomplished the whole training protocol. Compared with control group, subjects trained 3 times a week experienced an increase of parasympathetic activity (RMSSD value) by 58.3% ( P < 0.01) while global (SDNN) activity did not differ significantly. Subjects from the latter group also improved their 6 min walking distance by 12.0% ( P < 0.01). A nine-month brisk walking training enhances parasympathetic activity and improves walking distance in frail institutionalized old people. In that view physical activity may prevent cardiovascular risks and might help to reduce the loss of autonomy even after 80.