2 research outputs found
Derivation and validation of a 10-year risk score for symptomatic abdominal aortic aneurysm
BACKGROUND: Abdominal aortic aneurysm (AAA) can occur in patients who are ineligible for routine ultrasound screening. A
simple AAA risk score was derived and compared with current guidelines used for ultrasound screening of AAA.
METHODS: United Kingdom Biobank participants without previous AAA were split into a derivation cohort (n=401820, 54.6%
women, mean age 56.4 years, 95.5% White race) and validation cohort (n=83816). Incident AAA was defined as first hospital
inpatient diagnosis of AAA, death from AAA, or an AAA-related surgical procedure. A multivariable Cox model was developed in
the derivation cohort into an AAA risk score that did not require blood biomarkers. To illustrate the sensitivity and specificity of
the risk score for AAA, a theoretical threshold to refer patients for ultrasound at 0.25% 10-year risk was modeled. Discrimination
of the risk score was compared with a model of US Preventive Services Task Force (USPSTF) AAA screening guidelines.
RESULTS: In the derivation cohort, there were 1570 (0.40%) cases of AAA over a median 11.3 years of follow-up. Components
of the AAA risk score were age (stratified by smoking status), weight (stratified by smoking status), antihypertensive and
cholesterol-lowering medication use, height, diastolic blood pressure, baseline cardiovascular disease, and diabetes. In the
validation cohort, over 10 years of follow-up, the C-index for the model of the USPSTF guidelines was 0.705 (95% CI,
0.678–0.733). The C-index of the risk score as a continuous variable was 0.856 (95% CI, 0.837–0.878). In the validation
cohort, the USPSTF model yielded sensitivity 63.9% and specificity 71.3%. At the 0.25% 10-year risk threshold, the risk
score yielded sensitivity 82.1% and specificity 70.7% while also improving the net reclassification index compared with the
USPSTF model +0.176 (95% CI, 0.120–0.232). A combined model, whereby risk scoring was combined with the USPSTF
model, also improved prediction compared with USPSTF alone (net reclassification index +0.101 [95% CI, 0.055–0.147]).
CONCLUSIONS: In an asymptomatic general population, a risk score based on patient age, height, weight, and medical history
may improve identification of asymptomatic patients at risk for clinical events from AAA. Further development and validation
of risk scores to detect asymptomatic AAA are needed
Geographic variations in the PARADIGM-HF heart failure trial
AIMS: The globalization of clinical trials has highlighted geographic variations in patient characteristics, event rates, and treatment effects. We investigated these further in PARADIGM-HF, the largest and most globally representative trial in heart failure (HF) to date. METHODS AND RESULTS: We looked at five regions: North America (NA) 622 (8%), Western Europe (WE) 1680 (20%), Central/Eastern Europe/Russia (CEER) 2762 (33%), Latin America (LA) 1413 (17%), and Asia-Pacific (AP) 1487 (18%). Notable differences included: WE patients (mean age 68 years) and NA (65 years) were older than AP (58 years) and LA (63 years) and had more coronary disease; NA and CEER patients had the worst signs, symptoms, and functional status. North American patients were the most likely to have a defibrillating-device (53 vs. 2% AP) and least likely prescribed a mineralocorticoid receptor antagonist (36 vs. 61% LA). Other evidence-based therapies were used most frequently in NA and WE. Rates of the primary composite outcome of cardiovascular (CV) death or HF hospitalization (per 100 patient-years) varied among regions: NA 13.5 (95% CI 11.7-15.6), WE 9.6 (8.6-10.6), CEER 12.3 (11.4-13.2), LA 11.2 (10.0-12.5), and AP 12.5 (11.3-13.8). After adjustment for prognostic variables, relative to NA, the risk of CV death was higher in LA and AP and the risk of HF hospitalization lower in WE. The benefit of sacubitril/valsartan was consistent across regions. CONCLUSION: There were many regional differences in PARADIGM-HF, including in age, symptoms, comorbidity, background therapy, and event-rates, although these did not modify the benefit of sacubitril/valsartan. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255