Showing papers by "Kim A. Eagle published in 2009"

Diagnosis of Acute Aortic Dissection by D-Dimer The International Registry of Acute Aortic Dissection Substudy on Biomarkers (IRAD-Bio) Experience

Abstract: Background— D-dimer has been reported to be elevated in acute aortic dissection. Potential use as a “rule-out” marker has been suggested, but concerns remain given that it is elevated in other acute chest diseases, including pulmonary embolism and ischemic heart disease. We evaluated the diagnostic performance of D-dimer testing in a study population of patients with suspected aortic dissection. Methods and Results— In this prospective multicenter study, 220 patients with initial suspicion of having acute aortic dissection were enrolled, of whom 87 were diagnosed with acute aortic dissection and 133 with other final diagnoses, including myocardial infarction, angina, pulmonary embolism, and other uncertain diagnoses. D-dimer was markedly elevated in patients with acute aortic dissection. Analysis according to control disease, type of dissection, and time course showed that the widely used cutoff level of 500 ng/mL for ruling out pulmonary embolism also can reliably rule out aortic dissection, with a negat...

Acute Aortic Syndromes and Thoracic Aortic Aneurysm

Abstract: Acute and chronic aortic diseases have been diagnosed and studied by physicians for centuries. Both the diagnosis and treatment of aortic diseases have been steadily improving over time, largely because of increased physician awareness and improvements in diagnostic modalities. This comprehensive review discusses the pathophysiology and risk factors, classification schemes, epidemiology, clinical presentations, diagnostic modalities, management options, and outcomes of various aortic conditions, including acute aortic dissection (and its variants intramural hematoma and penetrating aortic ulcers) and thoracic aortic aneurysms. Literature searches of the PubMed database were conducted using the following keywords: aortic dissection, intramural hematoma, aortic ulcer, and thoracic aortic aneurysm. Retrospective and prospective studies performed within the past 20 years were included in the review; however, most data are from the past 15 years.

Does simplicity compromise accuracy in ACS risk prediction? A retrospective analysis of the TIMI and GRACE risk scores.

Abstract: Background The Thrombolysis in Myocardial Infarction (TIMI) risk scores for Unstable Angina/Non-ST–elevation myocardial infarction (UA/NSTEMI) and ST-elevation myocardial infarction (STEMI) and the Global Registry of Acute Coronary Events (GRACE) risk scores for in-hospital and 6-month mortality are established tools for assessing risk in Acute Coronary Syndrome (ACS) patients. The objective of our study was to compare the discriminative abilities of the TIMI and GRACE risk scores in a broad-spectrum, unselected ACS population and to assess the relative contributions of model simplicity and model composition to any observed differences between the two scoring systems. Methodology/Principal Findings ACS patients admitted to the University of Michigan between 1999 and 2005 were divided into UA/NSTEMI (n = 2753) and STEMI (n = 698) subpopulations. The predictive abilities of the TIMI and GRACE scores for in-hospital and 6-month mortality were assessed by calibration and discrimination. There were 137 in-hospital deaths (4%), and among the survivors, 234 (7.4%) died by 6 months post-discharge. In the UA/NSTEMI population, the GRACE risk scores demonstrated better discrimination than the TIMI UA/NSTEMI score for in-hospital (C = 0.85, 95% CI: 0.81–0.89, versus 0.54, 95% CI: 0.48–0.60; p<0.01) and 6-month (C = 0.79, 95% CI: 0.76–0.83, versus 0.56, 95% CI: 0.52–0.60; p<0.01) mortality. Among STEMI patients, the GRACE and TIMI STEMI scores demonstrated comparably excellent discrimination for in-hospital (C = 0.84, 95% CI: 0.78–0.90 versus 0.83, 95% CI: 0.78–0.89; p = 0.83) and 6-month (C = 0.72, 95% CI: 0.63–0.81, versus 0.71, 95% CI: 0.64–0.79; p = 0.79) mortality. An analysis of refitted multivariate models demonstrated a marked improvement in the discriminative power of the TIMI UA/NSTEMI model with the incorporation of heart failure and hemodynamic variables. Study limitations included unaccounted for confounders inherent to observational, single institution studies with moderate sample sizes. Conclusions/Significance The GRACE scores provided superior discrimination as compared with the TIMI UA/NSTEMI score in predicting in-hospital and 6-month mortality in UA/NSTEMI patients, although the GRACE and TIMI STEMI scores performed equally well in STEMI patients. The observed discriminative deficit of the TIMI UA/NSTEMI score likely results from the omission of key risk factors rather than from the relative simplicity of the scoring system.

Unprotected left main revascularization in patients with acute coronary syndromes

Abstract: Aims In acute coronary syndromes (ACS), the optimal revascularization strategy for unprotected left main coronary disease (ULMCD) has been little studied. The objectives of the present study were to describe the practice of ULMCD revascularization in ACS patients and its evolution over an 8-year period, analyse the prognosis of this population and determine the effect of revascularization on outcome. Methods and results Of 43 018 patients enrolled in the Global Registry of Acute Coronary Events (GRACE) between 2000 and 2007, 1799 had significant ULMCD and underwent percutaneous coronary intervention (PCI) alone ( n = 514), coronary artery bypass graft (CABG) alone ( n = 612), or no revascularization ( n = 673). Mortality was 7.7% in hospital and 14% at 6 months. Over the 8-year study, the GRACE risk score remained constant, but there was a steady shift to more PCI than CABG over time. Patients undergoing PCI presented more frequently with ST-segment elevation myocardial infarction (STEMI), after cardiac arrest, or in cardiogenic shock; 48% of PCI patients underwent revascularization on the day of admission vs. 5.1% in the CABG group. After adjustment, revascularization was associated with an early hazard of hospital death vs. no revascularization, significant for PCI (hazard ratio (HR) 2.60, 95% confidence interval (CI) 1.62–4.18) but not for CABG (1.26, 0.72–2.22). From discharge to 6 months, both PCI (HR 0.45, 95% CI 0.23–0.85) and CABG (0.11, 0.04–0.28) were significantly associated with improved survival in comparison with an initial strategy of no revascularization. Coronary artery bypass graft revascularization was associated with a five-fold increase in stroke compared with the other two groups. Conclusion Unprotected left main coronary disease in ACS is associated with high mortality, especially in patients with STEMI and/or haemodynamic or arrhythmic instability. Percutaneous coronary intervention is now the most common revascularization strategy and preferred in higher risk patients. Coronary artery bypass graft is often delayed and performed in lower risk patients, leading to good 6-month survival. The two approaches therefore appear complementary.

Characteristics and in-hospital outcomes of patients with cardiac tamponade complicating type A acute aortic dissection

Abstract: Cardiac tamponade (TMP) is a life-threatening complication of acute type A aortic dissection (AAD). The purpose of this study was to assess the clinical characteristics and in-hospital outcomes of TMP in the setting of AAD on the basis of the findings in the large cohort of the International Registry of Acute Aortic Dissection (IRAD). Six hundred seventy-four patients (mean age 61.8 +/- 14.2 years) with AAD in IRAD were studied. TMP was suspected on clinical grounds and confirmed by diagnostic imaging. Univariate testing was followed by multivariate logistic regression analysis to determine the association of TMP. TMP was detected in 126 patients with AAD (18.7%). Age did not differ between patients with and without TMP. Those with TMP less often had previous cardiac surgery (7.0% vs 17.1%, p = 0.007). Syncope (37.8% vs 13.7%, p <0.0001) and altered mental status (31.2% vs 10.6%, p <0.0001) were more common in patients with AAD with TMP than without TMP. Patients with TMP were more likely to have widened mediastina on chest x-ray (72.6% vs 60.3%, p = 0.02) and to have periaortic hematomas (44.7% vs 21.2%, p <0.0001). In-hospital outcomes were significantly worse in patients with TMP. The mortality of patients with TMP remained significantly higher, even after adjustment for baseline clinical characteristics (p <0.001). On logistic regression, altered mental status, hypotension, and early mortality were identified as independent correlates of TMP. In conclusion, TMP is not uncommon in patients with AAD. Syncope, altered mental status, and a widened mediastinum on chest x-ray on presentation suggest TMP, the presence of which warrants urgent operative therapy to improve outcome.

Temporal management patterns and outcomes of non-ST elevation acute coronary syndromes in patients with kidney dysfunction.

Abstract: Aims To examine: (i) the temporal changes in the management pattern; (ii) the reasons for any treatment disparities; (iii) the relationship between invasive treatment and outcome, among acute coronary syndrome (ACS) patients with vs. without kidney dysfunction. Methods and results Canadian ACS I, ACS II registries and Global Registry of Acute Coronary Events (GRACE) were prospective, multi-centre, observational studies of patients with ACS. From 1999 to 2007, non-ST elevation (NSTE) ACS patients were recruited in ACS I ( n = 3295; 1999–2001), ACS II ( n = 1956; 2002–2003), and GRACE ( n = 6491; 2004–2007) in Canada. Using the four-variable Modified Diet in Renal Disease equation, we stratified the study population ( n = 11 377) into three groups based on their estimated glomerular filtration rate (eGFR), and examined their treatment and outcome. While in-hospital use of coronary angiography and revascularization increased over time in all groups ( P < 0.001), patients with kidney dysfunction were less likely to undergo invasive management ( P < 0.001). Unadjusted 1 year mortality was lower among patients receiving in-hospital coronary angiography within all eGFR categories (≥60 mL/min/1.73 m2: 2.5 vs. 7.6%, P < 0.001; 30–59 mL/min/1.73 m2: 8.0 vs. 14.6%, P < 0.001; <30 mL/min/1.73 m2: 27.5 vs. 41.5%, P = 0.043). In-hospital revascularization was independently associated with lower 1-year mortality (adjusted OR = 0.52, 95% CI 0.36–0.77, P = 0.001), irrespective of eGFR ( P for heterogeneity = 0.39). Underestimation of patient risk was the most common barrier to an invasive treatment strategy. Conclusion Despite temporal increases in invasive management of NSTE‐ACS, patients with kidney dysfunction are more commonly treated conservatively, with an associated worse outcome. In-hospital revascularization was independently associated with improved survival, irrespective of eGFR. Randomized controlled trials involving patients with kidney dysfunction are needed to confirm whether more aggressive treatment will improve their poor outcome.

Predicting freedom from clinical events in non-ST-elevation acute coronary syndromes: the Global Registry of Acute Coronary Events

Abstract: Objective: To identify patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) with a low likelihood of any adverse in-hospital event. Design, setting and patients: Data were analysed from 24 097 patients with NSTEMI or unstable angina included in the Global Registry of Acute Coronary Events (January 2001 to September 2007). Main outcome measures: In-hospital events were myocardial infarction, arrhythmia, congestive heart failure or shock, major bleeding, stroke or death. Two-thirds of the patients were randomly chosen for model development and the remainder for model validation. Multiple logistic regression identified predictors of freedom from an in-hospital event, and a Freedom-from-Event score was developed. Results: Of the 16 127 patients in the model development group, 19.1% experienced an in-hospital adverse event. Fifteen factors independently predicted freedom from an adverse event: younger age; lower Killip class; unstable angina presentation; no hypotension; no ST deviation; no cardiac arrest at presentation; normal creatinine; decreased pulse rate; no hospital transfer; no history of diabetes, heart failure, peripheral arterial disease, or atrial fibrillation; prehospital use of statins, and no chronic warfarin. In the validation group, 18.6% experienced an adverse event. The model discriminated well between patients experiencing an in-hospital event and those who did not in both derivation and validation groups (c-statistic = 0.77 in both). Patients in the three lowest risk deciles had a very low in-hospital mortality ( 93% event-free in hospital). The model also predicted freedom from postdischarge events (death, myocardial infarction, stroke; c-statistic = 0.77). Conclusions: The GRACE Freedom-from-Event score can predict the in-hospital course of NSTE-ACS, and identifies up to 30% of the admitted population at low risk of death or any adverse in-hospital event.

Regional and practice variation in adherence to guideline recommendations for secondary and primary prevention among outpatients with atherothrombosis or risk factors in the United States: a report from the REACH Registry.

Abstract: Background:To reduce atherothrombosis-related morbidity and mortality, implementation of guideline-recommended therapies for primary and secondary prevention is necessary. Few data are available for outpatients in actual clinical practice, especially those without known heart disease treated by phys

Atrial fibrillation in patients with ischemic stroke: A population-based study.

Abstract: Background Atrial fibrillation is a major risk factor for ischemic stroke. However, the prognostic impact of atrial fibrillation among patients with stroke is not fully clarified. We compared patient characteristics, including severity of stroke and comorbidity, quality of in-hospital care and outcomes in a cohort of first-time ischemic stroke patients with and without atrial fibrillation. Methods Based on linkage of public medical databases, we did a population-based follow-up study among 3,849 stroke patients from the County of Aarhus, Denmark admitted in the period of 2003-2007 and prospectively registered in the Danish National Indicator Project. Results Atrial fibrillation was associated with an adverse prognostic profile but not with an overall poorer quality of in-hospital care. Patients with atrial fibrillation had a longer total length of stay (median: 15 vs 9 days), and were at increased risk of in-hospital medical complications (adjusted relative risk = 1.48, 95% CI: 1.23-1.79) and recurrent stroke (adjusted hazard ratio = 1.30, 95% CI: 0.93-1.82) when compared with patients without atrial fibrillation. The adjusted hazard ratios for 30 days and one year mortality were 1.55 (95% CI: 1.20-2.01) and 1.55 (95% CI: 1.30-1.85), respectively. Patients not eligible to oral anticoagulant treatment had an increased risk of recurrent stroke (adjusted hazard ratio = 1.92, 95% CI: 1.19-3.11). Conclusion Atrial fibrillation is associated with a poor outcome among patients with ischemic stroke particularly among patients, who are not eligible to oral anticoagulant treatment.

Childhood obesity: A comparison of health habits of middle-school students from two communities.

Abstract: OBJECTIVE: To assess whether children's diet and physical activity patterns differ between neighboring communities with differing resources. STUDY DESIGN AND SETTING: We compared the health behaviors of middle-school students in two Michigan communities; Ann Arbor and Ypsilanti; median household income of US$46,299 and 28,610, respectively. Self-reported diet and physical activity habits were collected. PARTICIPANTS: A total of 733 middle-school students from two neighboring communities (five Ann Arbor and two Ypsilanti middle schools) participated in the study. MEASURES: Data on age, gender, and racial/ethnic factors were collected as part of the baseline assessment. Students were also measured for height and weight. Body mass index was calculated. Information on diet and physical activity in addition to amounts and types of sedentary activities was assessed via questionnaires. RESULTS: More Ypsilanti schoolchildren were obese compared to the Ann Arbor schoolchildren (22.2% vs 12.6%; P = 0.01). The Ypsilanti schoolchildren reported higher consumption of fried meats (7.5% vs 3.2%; P = 0.02), French fries or chips (14.3% vs 7.9%; P = 0.02), punch or sports drinks (24.1% vs 12.2%; P = 0.001) and soda (18% vs 7.9%; P < 0.001) compared to the Ann Arbor children. School-based activities including physical education classes (58.6% vs 89.7%; P < 0.001) and sports teams (34.6% vs 62.8%; P < 0.001) differed for Ypsilanti schoolchildren vs Ann Arbor children. Sedentary behaviors were higher in the Ypsilanti children. CONCLUSIONS: Differences in diet and physical activity habits among children from two neighboring communities with varying resources suggests a need for school-based interventions to promote healthy behaviors among middle-school students.

Impact of prior statin therapy on arrhythmic events in patients with acute coronary syndromes (from the Global Registry of Acute Coronary Events [GRACE])

Abstract: Animal models of myocardial ischemia have demonstrated reduction in arrhythmias using statins. It was hypothesized that previous statin therapy before hospitalization might be associated with reductions of in-hospital arrhythmic events in patients with acute coronary syndromes. In this multinational, prospective, observational study (the Global Registry of Acute Coronary Events [GRACE]), data from 64,679 patients hospitalized for suspected acute coronary syndromes (from 1999 to 2007) were analyzed. The primary outcome of interest was in-hospital arrhythmic events in previous statin users compared with nonusers. The 2 primary end points were atrial fibrillation and the composite end point of ventricular tachycardia, ventricular fibrillation, and/or cardiac arrest. In-hospital death was also examined. Of the 64,679 patients, 17,636 (27%) had received previous statin therapy. Those taking statins had higher crude rates of histories of angina (69% vs 46%), diabetes (34% vs 22%), heart failure (15% vs 8.4%), hypertension (74% vs 58%), atrial fibrillation (9.3% vs 7.0%), and dyslipidemia (85% vs 35%). Patients previously taking statins were less likely to have in-hospital arrhythmias. In propensity-adjusted multivariable models, previous statin use was associated with a lower risk for ventricular tachycardia, ventricular fibrillation, or cardiac arrest (odds ratio 0.81, 95% confidence interval 0.72 to 0.96, p = 0.002); atrial fibrillation (odds ratio 0.81, 95% confidence interval 0.73 to 0.89, p <0.0001); and death (odds ratio 0.82, 95% confidence interval 0.70 to 0.95, p = 0.010). In conclusion, patients previously taking statins had a lower incidence of in-hospital arrhythmic events after acute coronary syndrome than those not previously taking statins. Our study suggests another possible benefit from appropriate primary and secondary prevention therapy with statins.

Is the Optimal Management of Acute Type A Aortic Intramural Hematoma Evolving

Abstract: Aortic intramural hematoma (IMH) has been considered a variant or precursor of aortic dissection with no entry tear or false lumen flow; however, the pathophysiological mechanism, risk factors, and evolution are rather different from those of classic dissection. Hematoma forms within the aortic wall as a result of either hemorrhage of the vasa vasorum or, less commonly, an intimal fracture of an atherosclerotic plaque. The marked relationship between IMH and atherosclerotic disease explains the older age of these patients compared with those with aortic dissection, the higher incidence of arterial hypertension, and the tendency for descending aorta involvement (50% to 60%).1–5 Article see p 2046 Evolution of the IMH in the acute phase may be highly dynamic, with bleeding of the aorta wall increasing progressively, stabilizing or provoking disruption of the intima, which may lead to a classic or localized dissection. This intimal disruption may be seen in the early hours of presentation or some months after the intramural bleeding has occurred2,5–8 (Figure 1). For this reason, IMH has been considered a precursor of aortic dissection. However, 2 significant differences between IMH and aortic dissection appear to be well defined. First, IMH might regress spontaneously with time4,5,7,9 (Figure 2). Second, fewer severe cardiovascular complications, valvular aortic regurgitation, and visceral or peripheral ischemia are present.2,8 Therefore, IMH almost resembles an aortic dissection, but with a distinct, unique pathological nature. Figure 1. Acute type A IMH (white arrows) with ascending aorta diameter of 45 mm and intramural thickness of 8 mm (left). After 6 days, the ascending aorta dissection was visualized. Black arrows show the intimal flap (right). Figure 2. Acute type A IMH (white arrow) with extension to descending aorta. Aortic diameter was 54 mm, and IMH thickness was 12 mm (left). After 6 months of medical …

Relation of body mass index to mortality after development of heart failure due to acute coronary syndrome.

Abstract: Several studies have suggested that obesity may be associated with a survival advantage in heart failure (HF). The duration of HF likely influences disease severity and may introduce lead-time bias into analyses of outcomes. The aim of this study was to analyze a cohort in which the exact time of HF onset could be determined: patients in the University of Michigan subset of the acute coronary syndromes (ACS) database of the Global Registry of Acute Coronary Events (GRACE) who developed new-onset HF (no history of HF and left ventricular ejection fraction ≤40% or qualitatively diminished) with their index ACS events from January 1999 to March 2006 (n = 446). For analysis, body mass index (BMI) was categorized as normal (18.5 to 2 ), overweight (25 to 2 ), and obese (≥30 kg/m 2 ). Underweight patients (BMI ≤18.5 kg/m 2 ) were excluded. Separate multivariate Cox regression models were performed to examine the effect of BMI group and other potential confounders on all-cause mortality and on the combined outcome of all-cause death, cardiac transplantation, or ventricular assist device implantation. BMI groups were not associated with different risks for the combined outcome, although overweight BMI approached statistical significance for lower risk for the combined outcome. Overweight BMI was significantly associated with lower risk for all-cause death (hazard ratio 0.63, 95% confidence interval 0.42 to 0.94, p = 0.02), although obese BMI was not (hazard ratio 1.06, 95% confidence interval 0.69 to 1.64, p = 0.8). In conclusion, these findings suggest a U-shaped relation between mortality and BMI in the setting of new-onset HF after ACS.

Prognostic Value of Admission Fasting Glucose Levels in Patients With Acute Coronary Syndrome

Abstract: Data are limited regarding the best prognostic glucose measure for patients admitted for an acute coronary event. We examined the admission fasting glucose levels among patients with acute coronary syndrome (ACS) from the University of Michigan ACS registry. The glucose levels were grouped into 3 categories (≥70 to

Cardiovascular ischemic event rates in outpatients with symptomatic atherothrombosis or risk factors in the united states: insights from the REACH Registry

Abstract: Background Atherothrombosis, defined as coronary artery, cerebrovascular, and peripheral arterial disease, is the leading cause of death in the United States. Limited data are available from outpatient populations to describe contemporary cardiovascular ischemic event rates and associated use of risk reduction treatments in patients with clinically manifest, or at risk for, atherothrombosis. The REduction of Atherothrombosis for Continued Health (REACH) Registry is an international, prospective, observational study of patients with either documented atherothrombotic syndromes or 3 or more risk factors designed to fill this knowledge gap. Methods Baseline demographics and 1-year outcomes were evaluated for US patients enrolled in the REACH Registry. Multivariate analytic models were constructed using baseline characteristics to determine independent predictors of 1-year event rates. Results In the United States, 25,686 patients were enrolled into the registry. Among symptomatic patients (n = 19,069), 19% had disease in >or=1 arterial bed. As of July 2006, 1-year outcomes were available for 93.4% (n = 23,985) of patients. The composite cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke event rate was 4.3% for the overall population and highest in patients with triple bed disease (9.9%). There was a relatively high use of risk reduction medications among symptomatic patients. However, opportunity for improvement remains. Approximately 9% of symptomatic patients were not using any antithrombotic, 7% were not using any antihypertensive agents, and 17% were not taking a lipid-lowering agent, whereas >80% of patients suffered from hypertension or dyslipidemia. Conclusions US patients with established atherothrombotic disease continue to experience high cardiovascular ischemic event rates; these rates increase in close association with polyvascular disease. Despite the use of risk reduction interventions, ideal secondary prevention of ischemic events has not been achieved.

Effects of a refugee elective on medical student perceptions

Abstract: There are growing numbers of refugees throughout the world. Refugee health is a relatively unstudied and rarely taught component of medical education. In response to this need, a Refugee Health Elective was begun. Medical student perceptions toward cultural aspects of medicine and refugee health before and after participation in the elective were measured. Preliminary questionnaires were given to all preclinical students at the academic year commencement with follow-up questionnaires at the refugee elective's conclusion. Both questionnaires examined students' comfort in interacting with patients and familiarity with refugee medical issues, alternative medical practices, and social hindrances to medical care. The preliminary answers served as a control and follow-up questionnaire data were separated into participant/non-participant categories. All preclinical medical students at two Midwestern medical schools were provided the opportunity to participate in the Refugee Health Elective and surveys. The 3 data groups were compared using unadjusted and adjusted analysis techniques with the Kruskall-Wallis, Bonferroni and ANCOVA adjustment. P-values < 0.05 were considered significant. 408 and 403 students filled out the preliminary and follow-up questionnaires, respectfully, 42 of whom participated in the elective. Students considering themselves minorities or multilingual were more likely to participate. Elective participants were more likely to be able to recognize the medical/mental health issues common to refugees, to feel comfortable interacting with foreign-born patients, and to identify cultural differences in understanding medical/mental health conditions, after adjusting for minority or multilingual status. As medical schools integrate a more multicultural curriculum, a Refugee Health Elective for preclinical students can enhance awareness and promote change in attitude toward medical/mental health issues common to refugees. This elective format offers tangible and effective avenues for these topics to be addressed.

Risk Factors in first presentation acute coronary syndromes (ACS): how do we move from population to individualized risk prediction?

Abstract: Patients with acute coronary syndromes (ACS) have a poor short- and long-term prognosis. We sought to examine the presence of established coronary risk factors in contemporary patients presenting with an ACS for the first time and no known coronary artery disease (CAD) in the past. The study was conducted in 3171 consecutive patients admitted with the diagnosis of ACS. Of these, 941 patients (30%) had the admission as the first occurrence of ACS and no prior history of CAD. We studied the degree to which these first presenters with ACS had 1 or more established risk factors. We found that 98% of patients presenting with an ACS for the first time and no previous CAD had at least 1 established risk factor. Current population-based screening efforts must be improved to allow more effective prevention strategies and more individualized risk prediction.