Dror Dicker

DPP-4 Inhibitors: Impact on glycemic control and cardiovascular risk factors

The first dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin was approved in 2006 as treatment for diabetes concurrently with lifestyle changes. A combined product of sitagliptin and glucophage was approved by the U.S. Food and Drug Administration in 2007. The second DPP-4 inhibitor, saxagliptin, was approved in the U.S. It was approved both as monotherapy as well as in combination with metformin, sulfonylurea, or thiazolidinedione. The use of a DPP-4 inhibitor called vildagliptin was approved in Europe and Latin America also as a combination with metformin, sulfonylurea, or thiazolidinedione. Two other DPP-4 inhibitors are also available (linagliptin and alogliptin). In this review, we will elaborate only on the first three drugs (sitagliptin, saxagliptin, and vildagliptin). The different DPP-4 inhibitors are distinctive in their metabolism (saxagliptin and vildagliptin are metabolized in the liver and sitagliptin is not), their excretion, their recommended dosage, and the daily dosage that is required for effective treatment. They are similar, however, when comparing their efficacy regarding lowering HbA1c levels, safety profile, and patient tolerance. The influence of DPP-4 inhibitors on the blood levels of HbA1c as monotherapy or in combination with other oral antidiabetes drugs was tested in multiple trials lasting 12–52 weeks. The results of these important trials were reviewed by Davidson (1) and will be summarized here briefly. Treatment with sitagliptin showed an average decrease in HbA1c levels of 0.65% after 12 weeks of treatment, 0.84% after 18 weeks of treatment, 0.85% after 24 weeks of treatment, 1.0% after 30 weeks of treatment, and 0.67% after 52 weeks of treatment. Treatment with saxagliptin showed an average decrease in HbA1c levels of 0.43–1.17%. Treatment with vildagliptin showed an average decrease in HbA1c levels of 1.4% after 24 weeks as monotherapy in a subgroup of patients with no prior oral treatment and …

Epicardial Adipose Tissue as a Predictor of Coronary Artery Disease in Asymptomatic Subjects

This study sought to elucidate the relation between epicardial adipose tissue (EAT) thickness measured by multidetector computed tomography and presence of coronary artery atherosclerosis. Recent studies have suggested that fat disposition in visceral organs and epicardial tissue could serve as a predictor of coronary artery disease (CAD). The sample included 190 asymptomatic subjects with ≥ 1 cardiovascular risk factor who were referred for cardiac computed tomographic angiography. Body mass index, blood pressure, fasting glucose level, and lipid profile were measured. Multidetector computed tomographic results were analyzed for atherosclerosis burden, calcium Agatston score, and EAT thickness: mean EAT values were 3.54 ± 1.59 mm in patients with atherosclerosis and 1.85 ± 1.28 mm in patients without atherosclerosis (p <0.001). On receiver operating characteristic analysis, an EAT value ≥ 2.4 mm predicted the presence of significant (>50% diameter) coronary artery stenosis. There was a significant difference in EAT values between patients with and without metabolic syndrome (2.58 ± 1.63 vs 2.04 ± 1.46 mm, p <0.05) and between patients with a calcium score >400 and <400 (3.38 ± 1.58 vs 2.02 ± 1.42 mm, p <0.0001). In conclusion, asymptomatic patients with CAD have significantly more EAT than patients without CAD. An EAT thickness of 2.4 mm is the optimal cutoff for prediction of presence of significant CAD.

Blood pressure and low-density lipoprotein-cholesterol lowering for prevention of strokes and cognitive decline: a review of available trial evidence.

Background and objectives: It is well established by a large number of randomized controlled trials that lowering blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) by drugs are powerful means to reduce stroke incidence, but the optimal BP and LDL-C levels to be achieved are largely uncertain. Concerning BP targets, two hypotheses are being confronted: first, the lower the BP, the better the treatment outcome, and second, the hypothesis that too low BP values are accompanied by a lower benefit and even higher risk. It is also unknown whether BP lowering and LDL-C lowering have additive beneficial effects for the primary and secondary prevention of stroke, and whether these treatments can prevent cognitive decline after stroke. Results: A review of existing data from randomized controlled trials confirms that solid evidence on optimal BP and LDL-C targets is missing, possible interactions between BP and LDL-C lowering treatments have never been directly investigated, and evidence in favour of a beneficial effect of BP or LDL-C lowering on cognitive decline is, at best, very weak. Conclusion: A new, large randomized controlled trial is needed to determine the optimal level of BP and LDL-C for the prevention of recurrent stroke and cognitive decline.

Continuation of the ESH-CHL-SHOT trial after publication of the SPRINT: rationale for further study on blood pressure targets of antihypertensive treatment after stroke.

Alberto Zanchetti, Lisheng Liu, Giuseppe Mancia, Gianfranco Parati, Guido Grassi, Marco Stramba-Badiale, Vincenzo Silani, Grzegorz Bilo, Giovanni Corrao, Antonella Zambon, Lorenza Scotti, Xinhua Zhang, Ting Rui Guan, Yuqing Zhang, Xuezhong Zhang, Eivind Berge, Josep Redon, Krzysztof Narkiewicz, Anna Dominiczak, Peter Nilsson, Margus Viigimaa, Stéphane Laurent, Enrico Agabiti-Rosei, Zhaosu Wu, Dingliang Zhu, José Luis Rodicio, Luis Miguel Ruilope, Nieves Martell-Claros, Fernando Pinto Roland E. Schmieder, Michel Burnier, Maciej Banach, Renata Cifkova, Csaba Farsang, Alexandra Konradi, Irina Lazareva, Yuriy Sirenko, Maria Dorobantu, Arman Postadzhiyan, Rok Accetto, Bojan Jelakovic, Dragan Lovic, Athanasios J. Manolis, Philippos Stylianou, Dror Dicker, Gangzhi Wei, Chengbin Xu, Hengge Xie, Antonio Coca, John O’Brien, Gary Ford, on behalf of the ESH-CHL-SHOT trial investigators

Interferon-induced vasospasm in chronic myeloid leukaemia.

The role of interferon (IFN) in the treatment of chronic myeloid leukaemia (CML) has been established. Many adverse effects have been reported, but vasospasm has been extremely rare. We report 2 CML patients who developed such complications. A 56-year-old female had been on IFN for 3 years with haematological and cytogenetic remission, when she developed an anginal syndrome followed by acute ischaemia. Coronary catheterization revealed normal arteries. After discontinuation of IFN her cardiac complaints disappeared and she needed no medication. A 61-year-old patient had been on IFN for 1 year when he presented with Raynaud’s phenomenon. No evidence of collagen vascular disease could be documented. IFN discontinuation and intravenous administration of iloprost (a prostacyclin analogue) resulted in the disappearance of the vascular complications. IFN appears to have a beneficial effect on the course and prognosis of CML. However, we have to be aware of the potential complications and adverse effects which can be related to IFN. Neither our experience nor the literature provides convincing recommendations regarding the management of such patients. We suggest proceeding with IFN at lower doses, especially in those who have achieved a cytogenetic response, as our first patient.

Increased Epicardial Adipose Tissue Thickness as a Predictor for Hypertension: A Cross-Sectional Observational Study

The aim of the study was to determine whether epicardial adipose tissue thickness (EAT), a new cardiometabolic risk factor, is associated with essential hypertension. The sample included 127 asymptomatic patients with one or more cardiovascular risk factors consecutively referred for cardiac computed tomography angiography. Data were collected retrospectively and compared between hypertensive (n=39) and normotensive (n=88) patients. The hypertensive patients had a significantly higher mean EAT thickness than the normotensive group (2.81±1.6 mm vs 2.07±1.43 mm; P=.011) and a significantly elevated mean coronary artery calcium score (316.8±512.6 vs 108.73±215; P=.0257). The odds ratio for a patient with tissue thickness ≥2.4 mm having hypertension was 1.396 (95% confidence interval, 1.033–1.922). Factors independently associated with hypertension were body mass index, low‐density lipoprotein, and age. A model score was developed using the logistic regression coefficients for calculation of individual risk. Hypertensive patients have significantly higher than normal EAT thickness. Epicardial adipose tissue thickness may serve as a risk indicator for hypertension and cardiovascular morbidity.

Association of Bariatric Surgery Using Laparoscopic Banding, Roux-en-Y Gastric Bypass, or Laparoscopic Sleeve Gastrectomy vs Usual Care Obesity Management With All-Cause Mortality

Importance Bariatric surgery is an effective and safe approach for weight loss and short-term improvement in metabolic disorders such as diabetes. However, studies have been limited in most settings by lack of a nonsurgical group, losses to follow-up, missing data, and small sample sizes in clinical trials and observational studies. Objective To assess the association of 3 common types of bariatric surgery compared with nonsurgical treatment with mortality and other clinical outcomes among obese patients. Design, Setting, and Participants Retrospective cohort study in a large Israeli integrated health fund covering 54% of Israeli citizens with less than 1% turnover of members annually. Obese adult patients who underwent bariatric surgery between January 1, 2005, and December 31, 2014, were selected and compared with obese nonsurgical patients matched on age, sex, body mass index (BMI), and diabetes, with a final follow-up date of December 31, 2015. A total of 33 540 patients were included in this study. Exposures Bariatric surgery (laparoscopic banding, Roux-en-Y gastric bypass, or laparoscopic sleeve gastrectomy) or usual care obesity management only (provided by a primary care physician and which may include dietary counseling and behavior modification). Main Outcomes and Measures The primary outcome, all-cause mortality, matched and adjusted for BMI prior to surgery, age, sex, socioeconomic status, diabetes, hyperlipidemia, hypertension, cardiovascular disease, and smoking. Results The study population included 8385 patients who underwent bariatric surgery (median age, 46 [IQR, 37-54] years; 5490 [65.5%] women; baseline median BMI, 40.6 [IQR, 38.5-43.7]; laparoscopic banding [n = 3635], gastric bypass [n = 1388], laparoscopic sleeve gastrectomy [n = 3362], and 25 155 nonsurgical matched patients (median age, 46 [IQR, 37-54] years; 16 470 [65.5%] women; baseline median BMI, 40.5 [IQR, 37.0-43.5]). The availability of follow-up data was 100% for all-cause mortality. There were 105 deaths (1.3%) among surgical patients during a median follow-up of 4.3 (IQR, 2.8-6.6) years (including 61 [1.7%] who underwent laparoscopic banding, 18 [1.3%] gastric bypass, and 26 [0.8%] sleeve gastrectomy), and 583 deaths (2.3%) among nonsurgical patients during a median follow-up of 4.0 (IQR, 2.6-6.2) years. The absolute difference was 2.51 (95% CI, 1.86-3.15) fewer deaths/1000 person-years in the surgical vs nonsurgical group. Adjusted hazard ratios (HRs) for mortality among nonsurgical vs surgical patients were 2.02 (95% CI, 1.63-2.52) for the entire study population; by surgical type, HRs were 2.01 (95% CI, 1.50-2.69) for laparoscopic banding, 2.65 (95% CI, 1.55-4.52) for gastric bypass, and 1.60 (95% CI, 1.02-2.51) for laparoscopic sleeve gastrectomy. Conclusions and Relevance Among obese patients in a large integrated health fund in Israel, bariatric surgery using laparoscopic banding, gastric bypass, or laparoscopic sleeve gastrectomy, compared with usual care nonsurgical obesity management, was associated with lower all-cause mortality over a median follow-up of approximately 4.5 years. The evidence of this association adds to the limited literature describing beneficial outcomes of these 3 types of bariatric surgery compared with usual care obesity management alone.

Practical Recommendations of the Obesity Management Task Force of the European Association for the Study of Obesity for the Post-Bariatric Surgery Medical Management

Bariatric surgery is today the most effective long-term therapy for the management of patients with severe obesity, and its use is recommended by the relevant guidelines of the management of obesity in adults. Bariatric surgery is in general safe and effective, but it can cause new clinical problems and is associated with specific diagnostic, preventive and therapeutic needs. For clinicians, the acquisition of special knowledge and skills is required in order to deliver appropriate and effective care to the post-bariatric patient. In the present recommendations, the basic notions needed to provide first-level adequate medical care to post-bariatric patients are summarised. Basic information about nutrition, management of co-morbidities, pregnancy, psychological issues as well as weight regain prevention and management is derived from current evidences and existing guidelines. A short list of clinical practical recommendations is included for each item. It remains clear that referral to a bariatric multidisciplinary centre, preferably the one performing the original procedure, should be considered in case of more complex clinical situations.

Blood pressure variability in acute ischemic stroke depends on hemispheric stroke location

The relationship between blood pressure (BP) variability and stroke location was examined in 85 patients admitted with acute ischemic stroke. The patients were divided into three groups according to stroke location: right hemisphere (32 patients), left hemisphere (30 patients) and non‐localized (23 patients). BP upon admission was 147.94/76.53±20.72/13.70 mmHg in the right hemisphere group, 151.81/76.10±25.69/16.23 mmHg in the left hemisphere and 155.23/83.41±30.45/15.74 in the non‐localized group. The left hemisphere group had significantly (p<0.01) greater variations in systolic and diastolic BP between days 2 and 3 and in systolic BP between days 3 and 4 after stroke compared with the other groups. BP in the left hemisphere group was less stable than in the other two groups. Non‐localized patients without pre‐existing hypertension had a significantly lower and more stable BP during the week following stroke than non‐localized patients with pre‐existing hypertension. Non‐localized patients with pre‐existing hypertension had the highest BP and showed no improvement during the week. Systolic BP tended to be higher and less stable in left hemisphere patients than in right hemisphere, whereas among non‐localized ischemic stroke patients BP was higher in those who had a prior diagnosis of hypertension.

Multidisciplinary rehabilitation program in recently hospitalized patients with heart failure and preserved ejection fraction: Rationale and design of a randomized controlled trial

BACKGROUND Heart failure with preserved ejection fraction (HFpEF) comprises a large portion of heart failure patients and portends poor prognosis with similar outcome to heart failure with reduced ejection fraction (HFrEF). Thus far, no medical therapy has been shown to improve clinical outcome in this common condition. TRIAL DESIGN The study is a randomized-controlled, multicenter clinical trial aimed to determine whether early posthospitalization comprehensive cardiac rehabilitation (CR) including exercise training (ET) in recently hospitalized HFpEF patients reduces the composite end point of all-cause mortality and hospitalizations in comparison with usual care (UC). After undergoing baseline evaluation, patients are randomized to either UC or to ambulatory comprehensive CR program. Patients in the CR arm will participate in a 6-month biweekly ET program according to a predefined protocol, in addition to a complementary home exercise prescribed by a specialist in CR. Exercise training will include endurance and low-intensity resistance training. Patients in the UC arm will be followed up at the outpatient clinic, with management according to current heart failure guidelines. Physician follow-up visits will be conducted at 3, 6, and 12 months for assessment of adherence to therapy and ET, functional status, quality of life, and clinical events. Secondary end points will include quality-of-life questionnaire, economic end points, blood pressure, and hemoglobin A1C levels. CONCLUSIONS Cardiac rehabilitation and ET are relatively inexpensive and accessible and can be beneficial in HFpEF patients. Our trial is designed to evaluate the impact of early posthospitalization comprehensive rehabilitation program on clinical end points of mortality, hospitalization, and quality of life in HFpEF patients.