Comparative effectiveness research (CER) aims to provide decision-makers the evidence needed to evaluate the benefits and harms of alternative clinical management strategies. CER has become a national priority, with considerable new research funding allocated. Cardiovascular disease is a priority area for CER. This workshop report provides an overview of CER methods, with an emphasis on practical clinical trials and observational treatment comparisons. The report also details recommendations to the National Heart Lung and Blood Institute for a new framework for evidence development to foster cardiovascular CER, and specific studies to address eight clinical issues identified by the Institute of Medicine as high priorities for cardiovascular CER.
comparative effectiveness; research methods; clinical trials
In the current issue of Population Health Metrics, two reports paint a bleak picture of American public health. Both physical inactivity and obesity remain highly prevalent; yet, it is not clear that increased physical activity will reduce the burden of obesity. There continue to be widespread disparities in life expectancy across United States counties. These reports appear against a backdrop of debate regarding how we should allocate our scarce resources for improving health: should we focus more on improving access to high-quality medical care, or should we instead focus on more and better public health interventions? While optimal solutions remain obscure, a look at prior successes suggests that ultimately they will come from the conduct and implementation of rigorous science, and in particular event-driven trials.
Public health; Population science; Obesity; Physical activity; Life-expectancy; Randomized trials
Over the past 60 years, revolutionary discoveries made by epidemiologists have contributed to marked declines in cardiovascular disease morbidity and mortality. Now, in an era of increasingly constrained resources, researchers in cardiovascular epidemiology face a number of challenges that call for novel, paradigm-shifting approaches. In this paper, the authors pose to the community 4 critical questions: 1) How can we avoid wasting resources on studies that provide little incremental knowledge? 2) How can we assure that we direct our resources as economically as possible towards innovative science? 3) How can we be nimble, responding quickly to new opportunities? 4) How can we identify prospectively the most meritorious research questions? Senior program staff at the National Heart, Lung, and Blood Institute invite the epidemiology community to join them in an ongoing Web-based blog conversation so that together we might develop novel approaches that will facilitate the next generation of high-impact discoveries.
cardiovascular diseases; epidemiology; National Institutes of Health (U.S.); research
Atrial fibrillation (AF) after cardiac surgery is a common marker of poor outcomes. Quantitative electrocardiographic (ECG) measurements may be valuable predictors of postoperative AF.
We evaluated clinical and ECG predictors of postoperative AF in 13,356 patients who underwent cardiac surgery in sinus rhythm.
4,724 patients (35%) developed postoperative AF. P-wave amplitude in lead aVR and V1 were the strongest ECG predictors. A less negative P-wave amplitude in lead aVR was associated with increased risk for postoperative AF (OR 1.46, CI 1.32–1.61), as was a more positive or a more negative P-wave amplitude in lead V1 (OR 1.25, CI 1.16–1.36) after adjusting for clinical and procedural predictors of postoperative AF. Reclassification analysis showed a 7% discrimination improvement (p<0.0001).
P-wave amplitude in lead aVR and lead V1 are powerful predictors of postoperative AF and in combination with other clinical predictors can guide application of prophylactic interventions.
editorials; exercise; risk, low; Framingham Risk Score; cardiovascular diseases
Chronic kidney disease (CKD) increases cardiovascular risk and mortality. However, traditional cardiovascular risk factors do not adequately account for the substantial increase in mortality observed in CKD. The aim of this study was to examine the relative contributions of novel cardiovascular risk factors to the risk between CKD and mortality. The study population included 4,680 consecutive new patients from a tertiary care preventive cardiology program from 1996 to 2005. Estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease (MDRD) method. Baseline levels of traditional (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, hypertension, triglycerides, total cholesterol, and fasting glucose) and emerging (apolipoproteins A-I and B, lipoprotein[a], fibrinogen, homocysteine, and high-sensitivity C-reactive protein) risk factors were examined. All-cause mortality was obtained from the Social Security Death Index. There were 278 deaths over a median follow-up period of 22 months. CKD (estimated glomerular filtration rate ≤60 ml/min/1.73 m2) was strongly associated with mortality after adjusting for traditional cardiovascular risk factors (hazard ratio 2.31, 95% confidence interval 1.77 to 3.11, p <0.001) and with the addition of propensity score (hazard ratio 2.33, 95% confidence interval 1.75 to 3.10, p <0.001). Of all the traditional and emerging risk factors monitored, only the addition of homocysteine and fibrinogen significantly attenuated the association between CKD and mortality (adjusted hazard ratio 1.73, 95% confidence interval 1.23 to 2.34, p <0.001), explaining 38% of the attributable mortality risk from CKD. A significant interaction (p = 0.004) between homocysteine and estimated glomerular filtration rate was observed whereby the annual mortality rate in subjects with CKD with homocysteine <10 μmol/L (the bottom tertile) was similar to those with normal renal function (1% per year), whereas homocysteine levels ≥12.5 μmol/L (the top tertile) were associated with a sevenfold greater mortality risk. In conclusion, homocysteine and fibrinogen levels explain nearly 40% of the attributable mortality risk from CKD.
The increasing availability of personal genomic tests has led to discussions about the validity and utility of such tests and the balance of benefits and harms. A multidisciplinary workshop was convened by the National Institutes of Health and the Centers for Disease Control and Prevention to review the scientific foundation for using personal genomics in risk assessment and disease prevention and to develop recommendations for targeted research. The clinical validity and utility of personal genomics is a moving target with rapidly developing discoveries but little translation research to close the gap between discoveries and health impact. Workshop participants made recommendations in five domains: (1) developing and applying scientific standards for assessing personal genomic tests; (2) developing and applying a multidisciplinary research agenda, including observational studies and clinical trials to fill knowledge gaps in clinical validity and utility; (3) enhancing credible knowledge synthesis and information dissemination to clinicians and consumers; (4) linking scientific findings to evidence-based recommendations for use of personal genomics; and (5) assessing how the concept of personal utility can affect health benefits, costs, and risks by developing appropriate metrics for evaluation. To fulfill the promise of personal genomics, a rigorous multidisciplinary research agenda is needed.
behavioral sciences; epidemiologic methods; evidence-based medicine; genetics; genetic testing; genomics; medicine; public health
In July of 2008, the National Heart, Lung, and Blood Institute convened experts in noninvasive cardiovascular imaging, outcomes research, statistics, and clinical trials to develop recommendations for future randomized controlled trials of the use of imaging in: 1) screening the asymptomatic patient for coronary artery disease; 2) assessment of patients with stable angina; 3) identification of acute coronary syndromes in the emergency room; and 4) assessment of heart failure patients with chronic coronary artery disease with reduced left ventricular ejection fraction. This study highlights several possible trial designs for each clinical situation.
cardiovascular imaging; chest pain diagnosis; clinical trials
cardiovascular imaging; chest pain diagnosis; clinical trials