Intensity Of Medical Therapy Research Articles

Circulating Biomarkers for Cardiovascular Disease Risk Prediction in Patients With Cardiovascular Disease.

Cardiovascular disease (CVD) is the leading cause of death globally. Risk assessment is crucial for identifying at-risk individuals who require immediate attention as well as to guide the intensity of medical therapy to reduce subsequent risk of CVD. In the past decade, many risk prediction models have been proposed to estimate the risk of developing CVD. However, in patients with a history of CVD, the current models that based on traditional risk factors provide limited power in predicting recurrent cardiovascular events. Several biomarkers from different pathophysiological pathways have been identified to predict cardiovascular events, and the incorporation of biomarkers into risk assessment may contribute to enhance risk stratification in secondary prevention. This review focuses on biomarkers related to cardiovascular and metabolic diseases, including B-type natriuretic peptide, high-sensitivity cardiac troponin I, adiponectin, adipocyte fatty acid-binding protein, heart-type fatty acid-binding protein, lipocalin-2, fibroblast growth factor 19 and 21, retinol-binding protein 4, plasminogen activator inhibitor-1, 25-hydroxyvitamin D, and proprotein convertase subtilisin/kexin type 9, and discusses the potential utility of these biomarkers in cardiovascular risk prediction among patients with CVD. Many of these biomarkers have shown promise in improving risk prediction of CVD. Further research is needed to assess the validity of biomarker and whether the strategy for incorporating biomarker into clinical practice may help to optimize decision-making and therapeutic management.

Carotid occlusion is associated with more frequent neurovascular events than moderately severe carotid stenosis

ObjectiveAsymptomatic internal carotid artery occlusion (CO) presents a clinical dilemma, and presently, the natural history, stroke risk, and optimal management remain ill defined. This study compared outcomes, including neurovascular events (NVEs) and health care costs, between patients with CO and patients with asymptomatic carotid artery stenosis (CS). MethodsA prospectively maintained database was queried to identify patients with CO and CS with at least >50% carotid stenosis by duplex. We identified and reviewed 622 consecutive patients with asymptomatic carotid artery disease at one academic medical center between 2011 and 2013. Patients with CO (n = 97) were identified and propensity matched by age and gender in a 1:2 ratio with CS patients (n = 194) for further analyses. Univariate and multivariate models were used to analyze baseline characteristics, clinical variables, and 1-year follow-up data from the date of diagnosis. Multivariate analysis was performed by multiple linear regression modeling. Institutional Review Board approval was obtained. ResultsFollow-up data were available for 99% of matched patients. CO patients were younger (72 vs 75 years; P < .01) and more likely male (67% vs 53%; P = .01) compared with CS patients. After propensity matching, baseline characteristics were similar between groups, with a trend toward higher use of statin therapy among patients with CO. Antiplatelet therapy was used in 79% of patients with CS and in 74% of patients with CO (P = .45). The rate of NVE among CO patients was higher than among CS patients at 1 year of follow-up (14% vs 7%; P = .03). Among those with NVE, neither antiplatelet therapy (64% vs 77%; P = .49) nor statin therapy (86% vs 77%; P = .58) appeared to have a significant effect. Health care costs ($14,361 vs $12,142; P = .44) and hospital admission rate (63% vs 71%; P = .18) were similar between groups. Not surprisingly, the rate of vascular procedures was higher in the CS group (55% vs 27%; P = .04). ConclusionsPatients with asymptomatic CO experience more NVEs compared with similar patients with moderately severe CS. Further study of preventative strategies, including intensity of medical therapy, is warranted.

Persistence of 123I-mIBG Prognostic Capability in Relation to Medical Therapy in Heart Failure (from the ADMIRE-HF Trial)

123I-mIBG imaging has been evaluated to assess sympathetic function and prognosis in heart failure (HF). However, the effect of combined HF medical therapies on 123I-mIBG uptake and its prognostic significance has not been previously examined. This analysis examined the relation between the intensity of guideline-directed HF medical therapy and global 123I-mIBG cardiac uptake in the AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) database. A second objective was to investigate whether this guideline-based therapy, measured by total medication doses, had the expected effect on outcome, that is, that patients with higher 123I-mIBG cardiac uptake and more intensive medical therapy had the fewest outcome events. Three HF cardiologists developed an HF Medication Score (HFMS) to quantify adequacy of dosages of β blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers and mineralocorticoid receptor antagonists. A Cox model was used to investigate the predictive ability of the HFMS for mortality events during median 17months follow-up. Multiple regression and Cox models assessed the usefulness of the HFMS relative to the planar heart/mediastinum ratio (H/Mp) from 123I-mIBG imaging in prediction of an event and to characterize the interaction of HFMS and H/M in predicting an event. HFMS was not a significant predictor of all-cause or cardiac death in either univariate or multivariate Cox models; H/Mp was highly significant for both event categories (p <0.0001). Mean H/Mp did not differ among HFMS ranges 0 to 3, 4 to 6, and 7 to 9. However, within each category, the mean H/Mp for subjects with events was significantly lower than that of subjects without events, with the exception of cardiac mortality in those with highest scores. In conclusion, intensity of medical therapy is not predictive of short-term mortality in HF patients. H/Mp is a good predictor for both cardiac and overall mortality regardless of medical therapy levels.

Segmental sigmoid polyposis as a colonoscopic indicator of an ileosigmoid fistula in Crohn's ileitis.

Ileosigmoid fistulas (ISFs) are frequently undiagnosed prior to surgery. This study was designed to describe a polyp or cluster of polyps limited to the sigmoid colon as a marker of ISF in patients with ileitis. This novel finding will increase a gastroenterologist's opportunity to detect them preoperatively and their prognostic implication of worsening ileitis. The medical records of patients with Crohn's disease and ISF were reviewed to determine whether colonoscopy had revealed polyposis limited to the sigmoid colon and its frequency. Thirty-seven patients with Crohn's ileitis complicated by ISF were identified from our database. Twenty had one or more sigmoid polyps without polyps elsewhere in the colon suggesting the site of fistula exit. Fifteen of the patients had ISF and five had ileorectal fistula (IRF). The fistula was detected by various means, including colonoscopy, sigmoidoscopy, small bowel X-ray series, barium enema, computed tomography, and magnetic resonance enterography. The ISF was generally diagnosed prior to the recognition and significance of the segmental polyps. These polyps were inflammatory or hyperplastic on pathologic review. Most ISFs and IRFs are now found preoperatively by imaging and some are incidental surgical findings. The segmental sigmoid polyps that we describe should help the gastroenterologist to be suspicious of ISF. The polyps are a surrogate marker for the progression of the fistula and the underlying ileitis as they tend to appear after the fistula has matured and lead to increased intensity of medical therapy well before surgical intervention is required.

Abstract P110: Patterns and Intensity of Medical Therapy in Patients Undergoing Percutaneous Coronary Intervention

Background The COURAGE study compared the effectiveness of optimal medical therapy (OMT) with, or without, percutaneous coronary intervention (PCI), in stable coronary artery disease (CAD). Understanding the translation of the COURAGE findings into practice could inform other contemporary comparative effectiveness studies. Methods We compared use of OMT both pre-PCI and at the time of discharge from the procedure before, and after, COURAGE's publication. The analysis was restricted to stable CAD patients undergoing PCI in the ACC-NCDR database from 9/05 - 12/08. Pre-PCI OMT was calculated as being on all of the following: aspirin, beta blocker and statin. Post-PCI OMT required all of the following: aspirin or thienopyridine, beta blocker, statin, and angiotensin converting enzyme inhibitor or angiotensin receptor blocker, if applicable. Results There were 383,444 patients who met study criteria. Aggressive OMT was used pre-PCI in 43.5% of patients (n = 75,529) before COURAGE was published and in 44.3% (n = 92,878) afterwards (p&lt;0.0001; Figure). The use of aggressive OMT at discharge after PCI before, and after, COURAGE publication was 39.1% (n = 67,853) and 41.8% (n=87,524) (p&lt;0.0001). Conclusion Minimal increases (&lt;3%) in the aggressive use of OMT after the release of COURAGE suggest that 1) the benefits of PCI, which in COURAGE were coupled with the aggressive use of life-prolonging medications, may not be observed in routine clinical care, and 2) that there was little impact of the COURAGE results on clinical practice. Important opportunities exist to improve the clinical care of stable CAD patients and to increase the adoption of comparative effectiveness research.

Error in Figure in: Patterns and Intensity of Medical Therapy in Patients Undergoing Percutaneous Coronary Intervention

Error in Figure in: Patterns and Intensity of Medical Therapy in Patients Undergoing Percutaneous Coronary Intervention

Response to Letter Regarding Article, “Selecting a Noninvasive Imaging Study After an Inconclusive Exercise Test”

HomeCirculationVol. 123, No. 23Response to Letter Regarding Article, “Selecting a Noninvasive Imaging Study After an Inconclusive Exercise Test” Free AccessReplyPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReplyPDF/EPUBResponse to Letter Regarding Article, “Selecting a Noninvasive Imaging Study After an Inconclusive Exercise Test” Ron Blankstein and Adam D. DeVore Ron BlanksteinRon Blankstein Noninvasive Cardiovascular Imaging Program Departments of Medicine (Cardiovascular Division) and Radiology Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston, MA (Blankstein, DeVore) Search for more papers by this author and Adam D. DeVoreAdam D. DeVore Noninvasive Cardiovascular Imaging Program Departments of Medicine (Cardiovascular Division) and Radiology Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston, MA (Blankstein, DeVore) Search for more papers by this author Originally published14 Jun 2011https://doi.org/10.1161/CIRCULATIONAHA.110.017632Circulation. 2011;123:e633We thank Schuster et al for their interest in our clinician update article,1 and for their thoughtful comments. We believe that many low-risk patients who are able to exercise and have a normal baseline ECG can be effectively evaluated with exercise treadmill testing. In our institution, despite the availability of many advanced imaging modalities, exercise treadmill testing remains the most commonly performed initial test for this patient population, an approach that is also supported by current guidelines.2,3 Although we certainly agree that the diagnostic accuracy of ECG changes to detect ischemia is lower than other noninvasive techniques, it is important to note that there are other important data provided by this test such as functional capacity and exercise-induced symptoms. Notably, patients that can achieve ≥10 metabolic equivalents are extremely unlikely to have any ischemia and have an excellent prognosis.4With respect to choosing between anatomic and functional imaging tests, it is important to understand that, in many cases, these techniques offer complementary data,5 and that the initial choice of test relies on the patient's pretest probability of obstructive disease. However, it would be oversimplified, and therefore inaccurate, to state that all patients with an intermediate pretest probability of coronary artery disease should have a functional test. The category of intermediate-risk patients represents a very large and diverse group of patients, most of whom do not have obstructive coronary artery disease, and would thus have a negative functional test.6 Therefore, a test that will identify the presence or absence of coronary artery disease could be more likely to influence subsequent pharmacological and lifestyle therapies.We strongly agree that functional testing—whether performed by invasive or noninvasive techniques—should guide the decision regarding coronary revascularization. However, many patients referred for noninvasive imaging have no or only mild abnormalities. In these patients, the role and intensity of medical therapy could be influenced by the presence, extent, and severity of coronary artery disease. However, in higher-risk patients, or those who have known coronary artery disease, functional testing for ischemia will be most beneficial, because it can identify the potential benefit from coronary revascularization. Pertinent to the discussion of risk assessment, it is worthwhile pointing out that, in the case presented in our update, the patient had already undergone an exercise treadmill testing and did not have any high-risk features. The reassuring results of this test can therefore be used to modify the pretest probability before subsequent testing (ie, lower the likelihood of obstructive disease).In conclusion, we believe that further studies are needed to better identify which intermediate-risk patients are more likely to have obstructive disease (and therefore should be referred for functional imaging) versus which ones may benefit from initial testing with computed tomography angiography. It must also be recognized that risk prediction models are based on population-level studies, and therefore physicians—who must make decisions about individual patients—must incorporate their clinical judgment and patient preferences and comorbidities, as well, when selecting the most optimal test.Ron Blankstein, MDAdam D. DeVore, MD Noninvasive Cardiovascular Imaging Program Departments of Medicine (Cardiovascular Division) and Radiology Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston, MADisclosuresNone.

Patterns and Intensity of Medical Therapy in Patients Undergoing Percutaneous Coronary Intervention

The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) study, which provided optimal medical therapy (OMT) to all patients and demonstrated no incremental advantage of percutaneous coronary intervention (PCI) on outcomes other than angina-related quality of life in stable coronary artery disease (CAD), suggests that a trial of OMT is warranted before PCI. It is unknown to what degree OMT is applied before PCI in routine practice or whether its use increased after the COURAGE trial. To examine the use of OMT in patients with stable angina undergoing PCI before and after the publication of the COURAGE trial. An observational study of patients with stable CAD undergoing PCI in the National Cardiovascular Data Registry between September 1, 2005, and June 30, 2009. Analysis compared use of OMT, both before PCI and at the time of discharge, before and after the publication of the COURAGE trial. Optimal medical therapy was defined as either being prescribed or having a documented contraindication to all medicines (antiplatelet agent, β-blocker, and statin). Rates of OMT before PCI and at discharge (following PCI) between the 2 study periods. Among all 467,211 patients (173,416 before [37.1%] and 293,795 after [62.9%] the COURAGE trial) meeting study criteria, OMT was used in 206,569 patients (44.2%; 95% confidence interval [CI], 44.1%-44.4%) before PCI and in 303,864 patients (65.0%; 95% CI, 64.9%-65.2%) at discharge following PCI (P < .001). Before PCI, OMT was applied in 75,381 patients (43.5%; 95% CI, 43.2%-43.7%) before the COURAGE trial and in 131,188 patients (44.7%; 95% CI, 44.5%-44.8%) after the COURAGE trial (P < .001). The use of OMT at discharge following PCI before and after the COURAGE trial was 63.5% (95% CI, 63.3%-63.7%) and 66.0% (95% CI, 65.8%-66.1%), respectively (P < .001). Among patients with stable CAD undergoing PCI, less than half were receiving OMT before PCI and approximately two-thirds were receiving OMT at discharge following PCI, with relatively little change in these practice patterns after publication of the COURAGE trial.

Functional polymorphism of detoxification gene NQO1 predicts intensity of empirical treatment of childhood asthma

The management of moderate to severe childhood asthma remains empirical. Genotypic variation has been proposed as a way to tailor specific pharmaceutical regimens to individual patients. The objective of this study was to determine the factors associated with asthma treatment progression, including functional polymorphisms of phase II detoxification enzymes, demographics, and environmental factors. In a study of 120 asthmatic children cared for in a single pediatric pulmonary practice, intensity of medical treatment over the year prior was modeled as a function of null mutations of glutathione S transferase ( GST) M1 and T1, ile105val variant of GSTP1, and pro187ser variant of NAD(P)H:quinone oxidoreductase 1 ( NQO1). The model included demographics, medical information, and environmental factors obtained via questionnaire analyzed with multivariate logistic regression and artificial neural networks. Multivariate logistic regression with bootstrapped validation identified a polymorphic variant of NQO1 as significantly contributing to increasing the odds of receiving more aggressive medical therapy (odds ratio, 11.56; p = 0.0001). Parent income and education inversely correlated with medical treatment (odds ratio, 1.50; p = 0.001 and odds ratio, 0.375; p = 0.002, respectively). Age and reporting restricted physical activity due to asthma also impacted medical treatment (odds ratio, 0.63; p = 0.0001 and odds ratio, 5.90; p = 0.004, respectively). The optimism-adjusted discriminative ability ( c-index) of the model was 0.881 (close to Bayes optimum of 0.902) with 80% overall classification accuracy. Our study supports the role of NQO1 polymorphism as an important factor determining the intensity of medical therapy in asthmatic children after adjusting for significance relating to parental income and education level, age, and restricted physical activity. Asthmatic children with a functional polymorphism of NQO1 may require more intensive pharmaceutical treatment to effectively control their asthma.

Appropriateness of coronary revascularization for patients with chronic stable angina or following an acute myocardial infarction: multinational versus Dutch criteria.

We convened a multinational panel to develop appropriateness criteria for percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass graft (CABG). To assess the applicability of these criteria, we applied them to patients referred for coronary revascularization. Finally, to understand how multinational criteria may differ from criteria developed by a panel of physicians from one country, we compared the appropriateness ratings using the multinational panel's criteria and those made using similar criteria previously developed by a panel of Dutch physicians. We conducted a prospective survey and review of the medical records of 2363 consecutive patients presenting with chronic stable angina or following a myocardial infarction who were referred for PTCA (n=1137) or CABG (n= 1226) at ten Dutch hospitals performing coronary revascularization. Appropriateness was measured using two sets of criteria developed by: (1) a Dutch panel of cardiologists and cardiothoracic surgeons in 1991; and (2) a similarly composed European panel in 1998. More PTCA referrals were rated inappropriate by Dutch criteria compared with multinational criteria among both patients with chronic stable angina (34.8 versus 6.1%; P< 0.001) and those with a recent myocardial infarction (28.1 versus 0.9%; P< 0.001). Among those patients referred for bypass surgery, the Dutch criteria judged a greater proportion of cases inappropriate than multinational criteria did for patients with chronic stable angina (3.7 versus 1.5%, P< 0.001). The proportion of cases rated inappropriate for bypass surgery among patients following a myocardial infarction was similar between the two panels (3.9 versus 2.4%, respectively; P=0.40). After reclassifying the data for two of the clinical factors used in the appropriateness criteria (lesion morphology and intensity of medical therapy) based on evidence that appeared in the literature after the Dutch panel met, we found no significant differences between the Dutch and multinational panels' appropriateness ratings. While fewer cases were judged inappropriate using the multinational criteria compared with the Dutch criteria, the differences in ratings were related primarily to the clinical factors used by each panel. These findings support the review of appropriateness criteria, and other forms of clinical guidelines, to ensure that they are current with the clinical evidence before using them to assess clinical care. Developing such criteria using a multinational panel, in contrast to multiple single country panels, would be a more efficient use of resources.

Measuring the clinical consistency of panelists' appropriateness ratings: the case of coronary artery bypass surgery

Objective: To assess the clinical consistency of expert panelists' ratings of appropriateness for coronary artery bypass surgery. Design: Quantitative analysis of panelists' ratings. Participants: Nine physicians (three cardiothoracic surgeons, four cardiologists, and two internists) convened by RAND to establish criteria for the appropriateness of coronary artery bypass surgery. Main outcomes measures: Percentage of indication-pairs given clinically inconsistent ratings (i.e. higher rating assigned to one member of an indication-pair when rating should have been equal or lower). Results: In the final round of appropriateness ratings, among 1785 pairs of indications differing only on a single clinical factor (e.g., three-vessel vs. two-vessel stenosis), 6.6% were assigned clinically inconsistent ratings by individual panelists, but only 2.7% received inconsistent ratings from the panel as a whole (using the median panel rating as the criterion). Internists on the panel provided fewer inconsistent ratings (4.6%) than either cardiologists (7.8%) or cardiothoracic surgeons (6.3%) ( p<0.001). More inconsistencies were noted when the factor distinguishing otherwise identical indications was symptom severity (inconsistency rate, 13.2%) or intensity of medical therapy (13.2%) than when it was number of stenosed vessels (3.8%) or proximal left anterior descending (PLAD) involvement (1.9%). Contrary to expectations, panelists' inconsistency rates increased between the initial and final rounds of appropriateness ratings (from 3.9 to 6.6%, p<0.001). Panelists' mean ratings across indications were only weakly correlated with individual inconsistency rates ( r=0.18, p=ns). Conclusions: The RAND/UCLA method for assessing the appropriateness of coronary revascularization generally produces criteria that are clinically consistent. However, research is needed to understand the sources of panelists' inconsistencies and to reduce inconsistency rates further.

A century of home parenteral nutrition for Crohn's disease

During an 11-year period, 41 patients with Crohn's disease were placed on home parenteral nutrition (HPN) for a mean of 1,083 days (range: 33 to 3,258 days). Data were retrospectively analyzed to determine whether HPN had an effect on the course of their disease, i.e., on the number of operative procedures performed and the intensity of required medical therapy. Data represented information obtained during a total of 121 patient-years of HPN for Crohn's disease. The main indications for HPN were short bowel syndrome (66%) and high stoma output. Twenty-four of 41 patients (59%) underwent surgery for Crohn's disease during the course of HPN. There was no significant difference between the number of procedures performed per patient per year of Crohn's disease during pre-HPN and HPN periods (p greater than 0.25). Although there was no significant change in body weight, both serum albumin and transferrin levels increased during HPN (p less than 0.01 and p less than 0.01, respectively). Twenty-nine percent of patients were taking prednisone while on HPN, compared with 54% of patients during the pre-HPN period (p less than 0.01). HPN appeared to result in a significant improvement in the numerically assessed quality of life. During the HPN period, 24 patients had 1 or more HPN-related complications that required 1 to 13 hospital admissions (mean: 1.8). These complications included catheter sepsis in 19 patients, blocked or damaged catheters in 15 patients, and dehydration and/or electrolyte imbalance in 5 patients. Eight patients died, with 7% of deaths secondary to catheter-related sepsis. Although permanent HPN is associated with an identifiable morbidity and mortality and is not associated with a reduction in the frequency of surgery for Crohn's disease, benefits include a decrease in the intensity of medical therapy, an improvement in patients' nutritional state, and a significant perceived improvement in patients' quality of life. Without HPN, we believe all patients would have died secondary to malnutrition and/or dehydration.