Manan Pareek

Enhanced predictive capability of a 1-hour oral glucose tolerance test : A prospective population-based cohort study

OBJECTIVE To examine whether the 1-h blood glucose measurement would be a more suitable screening tool for assessing the risk of diabetes and its complications than the 2-h measurement. RESEARCH DESIGN AND METHODS We conducted a prospective population-based cohort study of 4,867 men, randomly selected from prespecified birth cohorts between 1921 and 1949, who underwent an oral glucose tolerance test with blood glucose measurements at 0, 1, and 2 h. Subjects were followed for up to 39 years, with registry-based recording of events. Discriminative abilities of elevated 1-h (≥8.6 mmol/L) versus 2-h (≥7.8 mmol/L) glucose for predicting incident type 2 diabetes, vascular complications, and mortality were compared using Kaplan-Meier analysis, Cox proportional hazards regression, and net reclassification improvement. RESULTS Median age was 48 years (interquartile range [IQR] 48–49). During follow-up (median 33 years [IQR 24–37]), 636 (13%) developed type 2 diabetes. Elevated 1-h glucose was associated with incident diabetes (hazard ratio 3.40 [95% CI 2.90–3.98], P < 0.001) and provided better risk assessment than impaired glucose tolerance (Harrell concordance index 0.637 vs. 0.511, P < 0.001). Addition of a 1-h measurement in subjects stratified by fasting glucose provided greater net reclassification improvement than the addition of a 2-h measurement (0.214 vs. 0.016, respectively). Finally, the 1-h glucose was significantly associated with vascular complications and mortality. CONCLUSIONS The 1-h blood glucose level is a stronger predictor of future type 2 diabetes than the 2-h level and is associated with diabetes complications and mortality.

The Clopidogrel-PPI Interaction: An Updated Mini-Review

Proton pump inhibitors (PPIs) are recommended in patients with prior upper gastrointestinal bleeding and considered appropriate in patients with multiple other risk factors who require dual antiplatelet treatment (DAPT). During the past few years, however, concerns have been raised about the potential for PPIs, especially omeprazole, to decrease the efficacy of clopidogrel, and both the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) have issued warnings regarding the concomitant use of these medications. A review of the literature revealed that the pharmacodynamic studies support an interaction, whereas the clinical evidence, which is mainly based on nonrandomized, observational studies and secondary analyses of randomized trials, is conflicting. We conclude that PPIs should be prescribed together with DAPT for patients in whom they are recommended according to the guidelines and for patients with other indications. With respect to omeprazole, current evidence does not allow clear recommendations to be provided.

Ticagrelor for patients with acute coronary syndromes: PLATOnic affair or lasting SWEDEHEART?

This editorial refers to ‘Outcomes in patients treated with ticagrelor or clopidogrel after acute myocardial infarction: experiences from SWEDEHEART registry’, by A. Sahlen et al. doi:10.1093/eurheartj/ehw284. For many years, a 12-month course of clopidogrel plus lifelong aspirin comprised the standard antiplatelet regimen in patients after an acute coronary syndrome (ACS). This recommendation originally stemmed from the randomized, placebo-controlled Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial, in which the use of clopidogrel significantly reduced the composite endpoint of cardiovascular death, myocardial infarction (MI), or stroke, at the cost of an increased risk of non-fatal major bleeding, in patients with non-ST-segment elevation ACS (NSTE-ACS).1 A prospectively designed substudy extended this benefit on ischaemic events to the subgroup of patients who underwent percutaneous coronary intervention (PCI).2 Theoretical limitations associated with the use of clopidogrel include its irreversible binding to the ADP P2Y12 receptor, the required hepatic transformation into the active metabolite, and variable platelet inhibition. Unlike clopidogrel, ticagrelor provides both reversible and more consistent ADP receptor inhibition, and there is no need for biotransformation as the active compound itself is ingested.3 Based on results from the Platelet Inhibition and Patient Outcomes (PLATO) study, contemporary European Society of Cardiology (ESC) guidelines clearly favour the use of ticagrelor over clopidogrel in patients with ACS (class I recommendation), regardless of whether an invasive strategy is used or not.4,5 The approach in the American College of Cardiology/American Heart Association (ACC/AHA) guidelines is slightly more conservative, with the preference of ticagrelor over clopidogrel being ‘reasonable’ (class IIa recommendation).6,7 Nevertheless, because of issues of cost, familiarity, and bleeding concerns, use of clopidogrel still remains common worldwide. This issue of the journal features an elegant report by Sahlen et al . from the Swedish Web-system …

Metabolic Surgery: Weight Loss, Diabetes, and Beyond

The alarming rise in the worldwide prevalence of obesity is paralleled by an increasing burden of type 2 diabetes mellitus. Metabolic surgery is the most effective means of obtaining substantial and durable weight loss in individuals with obesity. Randomized trials have recently shown the superiority of surgery over medical treatment alone in achieving improved glycemic control, as well as a reduction in cardiovascular risk factors. The mechanisms seem to extend beyond the magnitude of weight loss alone and include improvements in incretin profiles, insulin secretion, and insulin sensitivity. Moreover, observational data suggest that the reduction in cardiovascular risk factors translates to better patient outcomes. This review describes commonly used metabolic surgical procedures and their current indications and summarizes the evidence related to weight loss and glycemic outcomes. It further examines their potential effects on cardiovascular outcomes and mortality and discusses future perspectives.

Uncontrolled hypertension is associated with coronary artery calcification and electrocardiographic left ventricular hypertrophy: a case-control study.

We conducted a 1:2 matched case-control study in order to evaluate whether the prevalence of coronary artery calcium (CAC) and electrocardiographic left ventricular hypertrophy (LVH) or strain was higher in patients with uncontrolled hypertension than in subjects from the general population, and evaluate the association between CAC and LVH in patients with uncontrolled hypertension. Cases were patients with uncontrolled hypertension, whereas the controls were random individuals from the general population without cardiovascular disease. CAC score was assessed using a non-contrast computed tomographic scan. LVH was evaluated using the Sokolow–Lyon voltage combination and Cornell voltage-duration product, respectively. Associations between CAC, LVH and traditional cardiovascular risk factors were tested by means of ordinal, conditional and classic binary logistic regression models. We found that uncontrolled hypertension was independently associated with both an ordinal CAC score category (odds ratio (OR) 3.9 (95% CI, 1.6–9.1), P=0.002), the presence of CAC score>99 (OR 4.5 (95% CI, 1.4–14.7), P=0.01) and electrocardiographic LVH (OR 10.1 (95% CI, 3.4–30.2), P<0.001) on both univariate and multivariable analyses. There was, however, no correlation between CAC and LVH. The lack of an association between CAC and LVH suggests that they are markers of different complications of hypertension and may have independent predictive values. Patients with both CAC and LVH may be at higher risk than those in whom only one of these markers is present.

Prognostic implications of fasting plasma glucose in subjects with echocardiographic abnormalities

AIMS To examine whether baseline fasting plasma glucose (FPG) modifies the prognostic role of left ventricular (LV) mass, geometric pattern, and diastolic function, for prediction of cardiovascular morbidity and mortality. METHODS Population-based cohort study comprising of 1047 men and 456 women with preserved ejection fraction, included between 2002 and 2006, who underwent echocardiography based on groups defined by FPG, measured prior to echocardiography. The clinical endpoint was the composite of cardiovascular events and all-cause mortality, assessed through national and local registries. Cox proportional-hazards regression with interaction analysis was used to evaluate the risk associated with FPG and LV structure and function. RESULTS Median age was 67years, and 31% had impaired fasting glucose, 31% diabetes, 17% LV hypertrophy, and 40% diastolic dysfunction. During a median follow-up duration of 8.3years, 449 composite events occurred. FPG (hazard ratio (HR), 1.09 (95% confidence interval (CI): 1.05-1.13), P<0.001) and several markers of LV structure and function, including LV mass index (HR, 1.10 (95% CI: 1.06-1.15), P<0.001) and E/é (HR, 1.08 (95% CI 1.05-1.10), P<0.001) were associated with an increased risk of events. In the subgroup of 678 individuals without previous cardiovascular disease, who did not receive cardiovascular, anti-diabetic, or lipid-lowering medication, FPG significantly interacted with the association between concentric LV hypertrophy and event risk (P<0.001), and with the association between diastolic dysfunction and event risk (P=0.02), including grade 2 or 3 dysfunction (P=0.04). CONCLUSIONS Echocardiographic abnormalities were more strongly associated with an adverse prognosis among subjects with impaired fasting glucose or diabetes.

Impact of Age and Target-Organ Damage on Prognostic Value of 24-Hour Ambulatory Blood Pressure

Markers of target-organ damage and 24-hour ambulatory blood pressure (BP) measurement improve cardiovascular risk stratification. The prevalence of target-organ damage and raised BP increases with aging. The study aim was to evaluate the impact of age and target-organ damage on the prognostic value of ambulatory BP. Markers of target-organ damage and ambulatory BP were measured in 1408 healthy people aged 41 or 51 (middle-aged group), and 61 or 71 (older group) years. The primary outcome was cardiovascular events after 16 years of follow-up, with data obtained from national registries. The prognostic value of BP was evaluated with Cox regression models, adjusted for traditional risk factors and target-organ damage, including left ventricular mass, pulse wave velocity, carotid plaques, and urine albumin/creatinine ratio. A total of 323 events were observed. In comparison with traditional risk factors, adding systolic BP and presence of target-organ damage improved risk stratification by increasing concordance index from 0.711 to 0.728 (P=0.01). In middle-aged subjects with target-organ damage, increment in pulse pressure (hazard ratio, 1.70; 95% confidence interval, 1.31–2.21; P<0.01) and increment in average real variability (hazard ratio, 1.29; 95% confidence interval, 1.05–1.59; P=0.02) were associated with a greater risk of cardiovascular disease compared with subjects without target-organ damage: hazard ratio, 1.04 (95% confidence interval, 0.74–1.46; P=0.81); P for interaction, 0.02; and hazard ratio, 0.89 (95% confidence interval, 0.69–1.14; P=0.36); P for interaction, 0.01. Target-organ damage may be a marker of individual susceptibility to the harmful effects of pulse pressure and BP variability on the cardiovascular system in middle-aged individuals.

Antithrombotic strategies for preventing long-term major adverse cardiovascular events in patients with non-valvular atrial fibrillation who undergo percutaneous coronary intervention

ABSTRACT Introduction: Balancing the risk of recurrent ischemia and bleeding among patients with non-valvular atrial fibrillation who undergo percutaneous coronary intervention (PCI) is challenging. Postprocedural antithrombotic therapy aims to reduce the risk related to coronary artery disease, stent placement, and atrial fibrillation, with acceptable risks of bleeding. Areas covered: This review summarizes evidence and recommendations related to long-term antithrombotic strategies in such patients. An overview of the findings from recent meta-analyses and select observational studies is provided, and important completed and ongoing randomized trials are described in detail. Recommendations pertaining to treatment intensity and duration, including the choice of specific anticoagulant and antiplatelet agents, are given. Expert opinion: Triple therapy (oral anticoagulation with dual antiplatelet therapy) is associated with an increased bleeding risk compared with double therapy (oral anticoagulation with a single antiplatelet agent), but double therapy does not appear to be associated with an increased risk of recurrent ischemia or death. Completed trials make a compelling case for double therapy with clopidogrel, not aspirin, when compared with full-intensity triple antithrombotic therapy. We believe that double therapy with an anticoagulant and clopidogrel should generally be favored instead of triple antithrombotic therapy.

Oral Antidiabetic Agents and Cardiovascular Outcomes

Cardiovascular disease is the leading cause of morbidity and mortality among patients with type 2 diabetes; however, a direct protective effect of tight glycemic control remains unproven. In fact, until 2008, when concerns related to rosiglitazone prompted regulatory agencies to mandate assessment of cardiovascular safety of new antidiabetic agents, little was known about how these medications affected cardiovascular outcomes. Since then, there has been a considerable increase in the number of cardiovascular trials, which employ a noninferiority design and focus on high-risk populations to establish safety in the shortest time possible. In this article, we summarize the 4 major cardiovascular outcome trials of oral antidiabetic agents, completed so far. These include 3 dipeptidyl peptidase-4 inhibitors (saxagliptin, alogliptin, and sitagliptin) and 1 sodium-glucose cotransporter-2 inhibitor (empagliflozin). We briefly discuss potential mechanisms, limitations, and provide an overview of the ongoing studies in this field.

Gastroprotection with proton-pump inhibitors in high-risk cardiovascular patients: who to target and for how long?

Proton-pump inhibitors (PPIs) are widely prescribed to over 100 million patients worldwide annually, are commonly available over the counter, and are challenging to regulate. PPIs have been shown to reduce dual antiplatelet therapy-related dyspepsia [1] and clinically significant gastrointestinal (GI) bleeding [2] in patients with established coronary artery disease (CAD). However, multiple observational studies have suggested potential cardiovascular and non-cardiovascular side effects with long-term use of PPI therapy [3] and have raised concerns regarding overuse and inappropriate use of these agents [4]. In this editorial, we discuss (1) the mechanistic pathways linking PPI therapy with potential cardiovascular risk; (2) the selection of potential candidates and duration of PPI gastroprotection; and (3) the future steps to optimize gastroprotection in cardiovascular disease.