Electronic health records to facilitate clinical research

Electronic health records (EHRs) provide opportunities to enhance patient care, embed performance measures in clinical practice, and facilitate clinical research. Concerns have been raised about the increasing recruitment challenges in trials, burdensome and obtrusive data collection, and uncertain generalizability of the results. Leveraging electronic health records to counterbalance these trends is an area of intense interest. The initial applications of electronic health records, as the primary data source is envisioned for observational studies, embedded pragmatic or post-marketing registry-based randomized studies, or comparative effectiveness studies. Advancing this approach to randomized clinical trials, electronic health records may potentially be used to assess study feasibility, to facilitate patient recruitment, and streamline data collection at baseline and follow-up. Ensuring data security and privacy, overcoming the challenges associated with linking diverse systems and maintaining infrastructure for repeat use of high quality data, are some of the challenges associated with using electronic health records in clinical research. Collaboration between academia, industry, regulatory bodies, policy makers, patients, and electronic health record vendors is critical for the greater use of electronic health records in clinical research. This manuscript identifies the key steps required to advance the role of electronic health records in cardiovascular clinical research

the relationship between alcohol consumption and vascular complications and mortality in individuals with type 2 diabetes

OBJECTIVE Moderate alcohol consumption has been associated with a reduced risk of mortality and coronary artery disease. The relationship between cardiovascular health and alcohol use in type 2 diabetes is less clear. The current study assesses the effects of alcohol use among participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) trial. RESEARCH DESIGN AND METHODS The effects of alcohol use were explored using Cox regression models, adjusted for potential confounders. The study end points were cardiovascular events (cardiovascular death, myocardial infarction, and stroke), microvascular complications (new or worsening nephropathy or retinopathy), and all-cause mortality. RESULTS During a median of 5 years of follow-up, 1,031 (9%) patients died, 1,147 (10%) experienced a cardiovascular event, and 1,136 (10%) experienced a microvascular complication. Compared with patients who reported no alcohol consumption, those who reported moderate consumption had fewer cardiovascular events (adjusted hazard ratio [aHR] 0.83; 95% CI 0.72–0.95; P = 0.008), less microvascular complications (aHR 0.85; 95% CI 0.73–0.99; P = 0.03), and lower all-cause mortality (aHR 0.87; 96% CI 0.75–1.00; P = 0.05). The benefits were particularly evident in participants who drank predominantly wine (cardiovascular events aHR 0.78, 95% CI 0.63–0.95, P = 0.01; all-cause mortality aHR 0.77, 95% CI 0.62–0.95, P = 0.02). Compared with patients who reported no alcohol consumption, those who reported heavy consumption had dose-dependent higher risks of cardiovascular events and all-cause mortality. CONCLUSION In patients with type 2 diabetes, moderate alcohol use, particularly wine consumption, is associated with reduced risks of cardiovascular events and all-cause mortality

Association of Heart Failure With Outcomes Among Patients With Peripheral Artery Disease: Insights From EUCLID.

Background Peripheral artery disease (PAD) and heart failure (HF) are each independently associated with poor outcomes. Risk factors associated with new-onset HF in patients with primary PAD are unknown. Furthermore, how the presence of HF is associated with outcomes in patients with PAD is unknown. Methods and Results This analysis examined risk relationships of HF on outcomes in patients with symptomatic PAD randomized to ticagrelor or clopidogrel as part of the EUCLID (Examining Use of Ticagrelor in Peripheral Arterial Disease) trial. Patients were stratified based on presence of HF at enrollment. Cox models were used to determine the association of HF with outcomes. A separate Cox model was used to identify risk factors associated with development of HF during follow-up. Patients with PAD and HF had over twice the rate of concomitant coronary artery disease as those without HF. Patients with PAD and HF had significantly increased risk of major adverse cardiovascular events (hazard ratio [HR], 1.31; 95% CI, 1.13-1.51) and all-cause mortality (HR, 1.39; 95% CI, 1.19-1.63). In patients with PAD, the presence of HF was associated with significantly less bleeding (HR, 0.65; 95% CI, 0.45-0.96). Characteristics associated with HF development included age ≥66 (HR, 1.29; 95% CI, 1.18-1.40 per 5 years), diabetes mellitus (HR, 1.85; 95% CI, 1.41-2.43), and weight (bidirectionally associated, ≥76 kg, HR, 0.77; 95% CI, 0.64-0.93; <76 kg, HR, 1.12; 95% CI, 1.07-1.16). Conclusions Patients with PAD and HF have a high rate of coronary artery disease with a high risk for major adverse cardiovascular events and death. These data support the possible need for aggressive treatment of (recurrent) atherosclerotic disease in PAD, especially patients with HF

World regional differences in outcomes for patients with peripheral artery disease: Insights from the EUCLID trial

Regional variations exist in the epidemiology of peripheral artery disease (PAD), in comorbidities, use of secondary prevention, and outcomes. Large studies of these variations in worldwide populations are rare. The EUCLID (Examining Use of tiCagreLor In peripheral artery Disease) trial included 13,885 patients with PAD from four geographical regions (Central/South America, Europe, Asia, North America) and compared monotherapy with ticagrelor and clopidogrel. Inclusion criteria were either an ankle-brachial index < 0.80 or a prior revascularization. The primary efficacy endpoint was time to first occurrence of any event in the composite of cardiovascular death, myocardial infarction, or ischemic stroke and did not differ between the study arms. This post hoc analysis of EUCLID confirmed that regional differences occurred in the inclusion criteria with more prior revascularization in North America (73.9%) and Asia (72.5%) compared with Central/South America (34.0%) and Europe (51.6%). The characteristics of patients also differed. Prior amputation at baseline was most frequent in Central/South America (6.3%) compared with other regions (1.6-2.8%). A history of stroke was most common in Asia, coronary heart disease in North America, and diabetes in Central/South America compared with other regions. The incidence of outcomes in patients with PAD varied by region. North America had the highest rate of the primary combined endpoint (5.97 events/100 patient-years). Corresponding rates were 4.80, 3.95, and 3.87 for Asia, Europe, and Central/South America, respectively. Hospitalization for acute limb ischemia (events/100 patient-years) was most frequent in Europe (0.75) and North America (0.74) compared with Asia (0.60) and Central/South America (0.33). Adjustment for inclusion criteria and relevant PAD characteristics did not have a major impact on these regional differences. Further adjustment for concomitant disease, risk factors, and preventive medication modified the regional differences only marginally. In conclusion, substantial regional differences were found in cardiovascular and limb outcomes in patients with PAD and were not explained by variation in the category of included patients, concomitant disease, risk factors, and prevention. Such differences, which may be due to variation in other factors such as background population rates or clinical care, need to be considered when designing and interpreting large international studies (ClinicalTrials.gov Identifier: NCT01732822)

Association of Heart Failure With Outcomes Among Patients With Peripheral Artery Disease: Insights From EUCLID

Background Peripheral artery disease (PAD) and heart failure (HF) are each independently associated with poor outcomes. Risk factors associated with new-onset HF in patients with primary PAD are unknown. Furthermore, how the presence of HF is associated with outcomes in patients with PAD is unknown.Methods and Results This analysis examined risk relationships of HF on outcomes in patients with symptomatic PAD randomized to ticagrelor or clopidogrel as part of the EUCLID (Examining Use of Ticagrelor in Peripheral Arterial Disease) trial. Patients were stratified based on presence of HF at enrollment. Cox models were used to determine the association of HF with outcomes. A separate Cox model was used to identify risk factors associated with development of HF during follow-up. Patients with PAD and HF had over twice the rate of concomitant coronary artery disease as those without HF. Patients with PAD and HF had significantly increased risk of major adverse cardiovascular events (hazard ratio [HR], 1.31; 95% CI, 1.13-1.51) and all-cause mortality (HR, 1.39; 95% CI, 1.19-1.63). In patients with PAD, the presence of HF was associated with significantly less bleeding (HR, 0.65; 95% CI, 0.45-0.96). Characteristics associated with HF development included age >= 66 (HR, 1.29; 95% CI, 1.18-1.40 per 5 years), diabetes mellitus (HR, 1.85; 95% CI, 1.41-2.43), and weight (bidirectionally associated, >= 76 kg, HR, 0.77; 95% CI, 0.64-0.93; Conclusions Patients with PAD and HF have a high rate of coronary artery disease with a high risk for major adverse cardiovascular events and death. These data support the possible need for aggressive treatment of (recurrent) atherosclerotic disease in PAD, especially patients with HF.</p

Determinants of coronary flow reserve in non-diabetic patients with chest pain without myocardial perfusion defects

<div><p>Background</p><p>Microvascular dysfunction could be responsible for chest pain in patients without myocardial perfusion defects. We evaluated microvascular function using ultrasound-assessed coronary flow reserve (CFR) in patients with chest pain and normal myocardial perfusion scintigram. Secondly, we investigated association between cardiovascular parameters and decreased CFR in a sex specific manner.</p><p>Methods</p><p>A total of 202 (128 women) non-diabetic patients with chest pain and suspected myocardial ischemia, but without myocardial perfusion defects on myocardial perfusion scintigram, were enrolled and underwent CFR examination and blood sampling. All patients were followed-up for cardiovascular events. We used a supervised principal component analysis including 66 variables such as clinical parameters, ongoing medication, coronary artery disease history, lipids, metabolic parameters, inflammatory and other cardiovascular parameters.</p><p>Results</p><p>During a median follow-up time of 5.4 years, 25 cardiovascular events occurred; (men;18, women;7). Average CFR of the study cohort was 2.7±1.2 and 14% showed impaired CFR<2.0. In an adjusted Cox regression analysis, CFR<2.0 independently predicted event-free survival (HR:2.5, p = 0.033). In the supervised principal component analysis high insulin resistance assessed by Homeostatic model assessment for insulin resistance was the strongest biochemical marker associated with decreased CFR. Interestingly, upon sex specific multivariable linear regression analysis, the association was only significant in men (β = -0.132, p = 0.041) while systolic blood pressure remained an independent predictor in women (β = -0.009, p = 0.011).</p><p>Conclusions</p><p>In non-diabetic patients with chest pain without myocardial perfusion defects, low CFR has prognostic value for future cardiovascular events. Insulin resistance appears to be a marker for decreased CFR in men. Indeed, in the context of contribution of traditional risk factors in this patient population, the value of systolic blood pressure seems to be important in the women.</p></div

Coronary flow reserve predicts major cardiovascular events in non-diabetic patients with chest pain without myocardial perfusion defects.

<p>(A) In a Cox regression analysis, coronary flow reserve below the pathological cut of <2.0 provides an independent prognostic value predicting long-term cardiovascular events in a study population of non-diabetic patients with chest pain without myocardial perfusion defects (n = 202). (B) The prognostic value remains when excluding patients with previously known CAD (n = 168). CAD = coronary artery disease.</p

Patient recruitment flowchart over the study population.

<p>Flow chart for overview of patient recruitment in the current study. The study was performed at Sahlgrenska University Hospital, Gothenburg Sweden, during the years 2006–2008. CFR = coronary flow reserve.</p

The contribution of variables for explaining CFR-determination.

<p>(A) Shows the loadings of the OPLS describing the relationship between the 66 variables and CFR in both sexes (n = 202). Each variable generated a loading value, p(1), along the principal component describing CFR. A positive loading value means that the variable is positively correlated to CFR and vice versa for a negative value. The error bars represent the 95% CI for the variable, and loadings representing variables of which variability is within the 95% CI are highlighted in grey. Dark grey represents plasma blood biomarkers (HOMA-IR, insulin, hyperlipidemia, HbA_1c, glucose, osteopontin and eosinophil counts). (B) Shows the distribution of men and women along the principal component describing CFR. A high score represents an individual with high CFR and vice versa. The box represents the median and the 25 to 75th percentiles and the whiskers min and max. Each individual is represented by black circle. CFR = coronary flow reserve, HbA_1c = glycosylated hemoglobin, HOMA-IR = homeostasic model assessment of insulin resistance, OPLS = orthogonal projection to latent structures by partial least square analysis.</p