Haptoglobin Phenotype Modifies the Influence of Intensive Glycemic Control on Cardiovascular Outcomes.

Background: Whereas there exists a direct relationship between glycated hemoglobin and cardiovascular disease (CVD), clinical trials targeting glycated hemoglobin to near-normal levels using intensive therapy have failed to prevent CVD and have even increased mortality, making clinical decision making difficult. A common polymorphism at the haptoglobin (Hp) genetic locus is associated with CVD, especially coronary heart disease, in the setting of hyperglycemia.

Objectives: This study sought to determine whether the treatment difference of intensive versus standard glucose-lowering therapy on risk of CVD events in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study depended on Hp phenotype.

Association of Fenofibrate Therapy With Long-term Cardiovascular Risk in Statin-Treated Patients With Type 2 Diabetes.

Importance: Patients with type 2 diabetes are at high risk of cardiovascular disease (CVD) in part owing to hypertriglyceridemia and low high-density lipoprotein cholesterol. It is unknown whether adding triglyceride-lowering treatment to statin reduces this risk.

Objective: To determine whether fenofibrate reduces CVD risk in statin-treated patients with type 2 diabetes.

Fibroblast growth factor 23 and incident CKD in type 2 diabetes.

Background And Objectives: High levels of fibroblast growth factor 23 are associated with accelerated progression of CKD. Whether high fibroblast growth factor 23 levels also predict incident CKD is uncertain.

Design, Setting, Participants, & Measurements: A prospective case-cohort study was conducted within the Action to Control Cardiovascular Risk in Diabetes Trial.

Paradoxical reduction in HDL-C with fenofibrate and thiazolidinedione therapy in type 2 diabetes: the ACCORD Lipid Trial.

Objective: To determine the occurrence of extremely low HDL cholesterol (HDL-C) among participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Trial and to examine the relationship of this finding with treatment with fenofibrate and thiazolidinedione (TZD).

Research Design And Methods: The ACCORD Lipid Trial was a randomized, double-blind, placebo-controlled study conducted in patients with type 2 diabetes at 77 clinical centers across the U.S.

Effects of randomization to intensive glucose control on adverse events, cardiovascular disease, and mortality in older versus younger adults in the ACCORD Trial.

Objective: We explore the effect of randomized treatment, comparing intensive to standard glucose-lowering strategies on major cardiovascular outcomes, death, and severe adverse events in older versus younger participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

Research Design And Methods: Participants with type 2 diabetes (n = 10,251) with a mean age of 62 years, a median duration of diabetes of 10 years, and a median A1C of 8.1% (65 mmol/mol) were randomized to treatment strategies targeting either A1C <6.

Long-term effects of intensive glucose lowering on cardiovascular outcomes.

Background: Intensive glucose lowering has previously been shown to increase mortality among persons with advanced type 2 diabetes and a high risk of cardiovascular disease. This report describes the 5-year outcomes of a mean of 3.7 years of intensive glucose lowering on mortality and key cardiovascular events.

Epidemiologic relationships between A1C and all-cause mortality during a median 3.4-year follow-up of glycemic treatment in the ACCORD trial.

Objective: Randomized treatment comparing an intensive glycemic treatment strategy with a standard strategy in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was ended early because of an unexpected excess of mortality in the intensive arm. As part of ongoing post hoc analyses of potential mechanisms for this finding, we explored whether on-treatment A1C itself had an independent relationship with mortality.

Research Design And Methods: Participants with type 2 diabetes (n = 10,251 with mean age 62 years, median duration of diabetes 10 years, and median A1C 8.

Effects of combination lipid therapy in type 2 diabetes mellitus.

Background: We investigated whether combination therapy with a statin plus a fibrate, as compared with statin monotherapy, would reduce the risk of cardiovascular disease in patients with type 2 diabetes mellitus who were at high risk for cardiovascular disease.

Methods: We randomly assigned 5518 patients with type 2 diabetes who were being treated with open-label simvastatin to receive either masked fenofibrate or placebo. The primary outcome was the first occurrence of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes.

Effects of intensive blood-pressure control in type 2 diabetes mellitus.

Background: There is no evidence from randomized trials to support a strategy of lowering systolic blood pressure below 135 to 140 mm Hg in persons with type 2 diabetes mellitus. We investigated whether therapy targeting normal systolic pressure (i.e.

The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study.

Objective: To determine whether there is a link between hypoglycaemia and mortality among participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

Design: Retrospective epidemiological analysis of data from the ACCORD trial. Setting Diabetes clinics, research clinics, and primary care clinics.

Constructing common cohorts from trials with overlapping eligibility criteria: implications for comparing effect sizes between trials.

Background: Comparing findings from separate trials is necessary to choose among treatment options, however differences among study cohorts may impede these comparisons.

Purpose: As a case study, to examine the overlap of study cohorts in two large randomized controlled clinical trials that assess interventions to reduce risk of major cardiovascular disease events in adults with type 2 diabetes in order to explore the feasibility of cross-trial comparisons

Methods: The Action for Health in Diabetes (Look AHEAD) and The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trials enrolled 5145 and 10,251 adults with type 2 diabetes, respectively. Look AHEAD assesses the efficacy of an intensive lifestyle intervention designed to produce weight loss; ACCORD tests pharmacological therapies for control of glycemia, hyperlipidemia, and hypertension.

Effects of intensive glucose lowering in type 2 diabetes.

Background: Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes. We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors.

Methods: In this randomized study, 10,251 patients (mean age, 62.

Prevention of cardiovascular disease in persons with type 2 diabetes mellitus: current knowledge and rationale for the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

Patients with type 2 diabetes mellitus die of cardiovascular disease (CVD) at rates 2-4 times higher than patients without diabetes but with similar demographic characteristics. The prevalence of diabetes is increasing in the United States and, thus, the prevention of CVD in patients with diabetes poses an urgent public health challenge. The objective of this report is to review the current knowledge base for the prevention of CVD in patients with diabetes, with particular emphasis on the control of glycemia, lipids, and blood pressure.

Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods.

Most patients with type 2 diabetes mellitus develop cardiovascular disease (CVD), with substantial loss of life expectancy. Nonfatal CVD contributes greatly to excess healthcare costs and decreased quality of life in patients with diabetes. The current epidemic of obesity has raised expectations that CVD associated with type 2 diabetes will become an even greater public health challenge.

Lessons learned from the prospective pravastatin pooling project.

The Prospective Pravastatin Pooling (PPP) Project was a prospectively defined collaboration of three randomized, placebo-controlled, long-term, monotherapy (40 mg/d) trials of the lipid-lowering agent pravastatin. A pooled database of 19,768 participants with a mean of 5.2 years of follow-up was created, providing the investigators with over 100,000 patient-years of experience to address questions on total and cause-specific mortality, coronary incidence, stroke, and safety.

Additive benefits of pravastatin and aspirin to decrease risks of cardiovascular disease: randomized and observational comparisons of secondary prevention trials and their meta-analyses.

Background: In randomized trials of secondary prevention, pravastatin sodium and aspirin reduce risks of cardiovascular disease. Pravastatin has a predominantly delayed antiatherogenic effect, and aspirin has an immediate antiplatelet effect, raising the possibility of additive clinical benefits.

Methods: In 5 randomized trials of secondary prevention with pravastatin (40 mg/d), comprising 73 900 patient-years of observation, aspirin use was also prescribed in varying frequencies, and data were available on a large number of confounding variables.

Pregnancy-related death and health care services.

Objective: To examine the association between health care services variables and pregnancy-related death using a contemporary geographically defined population and enhanced methods for case identification.

Methods: This is a population-based, case-control study from North Carolina for the 7-year period 1992-1998. Pregnancy-related deaths after a live birth (n = 118) were identified after review of pregnancy-associated deaths (n = 400) ascertained from death certificate codes and linkage of birth and death files.

Effect of estrogen plus progestin on progression of carotid atherosclerosis in postmenopausal women with heart disease: HERS B-mode substudy.

Objective: The Heart and Estrogen/Progestin Replacement Study (HERS) found no overall effect of estrogen plus progestin (compared with placebo) on coronary event rates in 2763 postmenopausal women with established coronary disease (mean 4.1 years of follow-up). In addition to the events trial, a carotid ultrasound substudy was established in 1993 to be conducted concurrently to determine whether hormone therapy affects the progression of the underlying atherosclerotic process.

Safety and tolerability of pravastatin in long-term clinical trials: prospective Pravastatin Pooling (PPP) Project.

Background: Therapeutic decisions regarding pharmacological therapy should be based on safety and tolerability as well as efficacy data. Clinical trials designed to assess efficacy are often insufficiently powered to generate reliable safety data.

Methods And Results: The West of Scotland Coronary Prevention Study (WOSCOPS), the Cholesterol and Recurrent Events (CARE), and Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) studies collectively accumulated >112 000 person-years of exposure in double-blind randomized trials comparing placebo and pravastatin (40 mg once daily).