Asymptomatic High-risk Population Research Articles

A Stool DNA-Based SDC2 Methylation Test for the Early Detection of Colorectal Cancer in an Asymptomatic, High-Risk Population: A Multicenter Prospective Randomized Trial.

Noninvasive stool DNA-based methylation testing has emerged as an effective strategy for the early colorectal cancer (CRC) detection. Syndecan-2 (SDC2) methylation frequently occurs in all stages of CRC; therefore, the aim of this study was to evaluate the clinical performance of a stool DNA-based SDC2 methylation test for detecting CRC in asymptomatic or high-risk CRC populations. This multicenter prospective study was conducted to determine the clinical performance of the SDC2 methylation test on stool DNA using real-time polymerase chain reaction. Stool samples were collected from asymptomatic individuals before colonoscopy, and the test results were independently analyzed through comparison with colonoscopic findings and pathological outcomes as reference standards. Of the 1,124 evaluable participants, 20 had CRC, 73 had advanced adenomatous polyps (≥1.0 cm), 469 had nonadvanced adenomatous polyps (<1.0 cm), 178 had non-neoplastic polyps, and 384 had negative colonoscopy results. The stool SDC2 methylation test had a sensitivity and specificity of 95.0% and 81.5%, respectively, for detecting CRC, while the sensitivity for detecting advanced adenomatous polyps and CRC was 58.1%. The rate of adenoma detection increased with polyp size (P < 0.01), and sensitivity was not associated with CRC stage (P = 0.864). The stool DNA-based SDC2 methylation test attained a high sensitivity for CRC detection in an asymptomatic high-risk population. Further large-scale clinical studies are required to validate the clinical utility of this test as a population-based CRC screening tool.

Shall We Screen Lung Cancer with Volume Computed Tomography in Austria? A Cost-Effectiveness Modelling Study.

This study assessed the cost-effectiveness of a lung cancer screening (LCS) program using low-dose computed tomography (LDCT) in Austria. An existing decision tree with an integrated Markov model was used to analyze the cost-effectiveness of LCS versus no screening from a healthcare payer perspective over a lifetime horizon. A simulation was conducted to model annual LCS for an asymptomatic high-risk population cohort aged 50-74 with a smoking history using the Dutch-Belgian Lung Cancer Screening Study (NEderlands-Leuvens Longkanker ScreeningsONderzoek, NELSON) screening outcomes. The principal measure utilized to assess cost-effectiveness was the incremental cost-effectiveness ratio (ICER). Sensitivity and scenario analyses were employed to determine uncertainties surrounding the key model inputs. At an uptake rate of 50%, 300,277 eligible individuals would participate in the LCS program, yielding 56,122 incremental quality-adjusted life years (QALYs) and 84,049 life years gained compared to no screening, with an ICER of EUR 24,627 per QALY gained or EUR 16,444 per life-year saved. Additionally, LCS led to the detection of 25,893 additional early-stage lung cancers and averted 11,906 premature lung cancer deaths. It was estimated that LCS would incur EUR 945 million additional screening costs and EUR 386 million additional treatment costs. These estimates were robust in sensitivity analyses. Implementation of annual LCS with LDCT for a high-risk population, using the NELSON screening outcomes, is cost-effective in Austria, at a threshold of EUR 50,000 per QALY.

Prospective screening for monkeypox infection among users of HIV pre-exposure prophylaxis in Denmark.

During the 2022 outbreak of mpox (previously called monkeypox), which primarily affected Gay, Bisexual, and other Men who have Sex with Men (GBMSM), testing was mainly limited to individuals with symptoms of infection. Although sporadic cases of mpox continue to be diagnosed in Denmark, the feasibility of screening asymptomatic high-risk populations, such as those using HIV pre-exposure prophylaxis (PrEP), is still unknown. During the autumn of 2022, a rectal swab test for mpox PCR was included in the routine sexually transmitted infections (STI) screening for PrEP users. The screening included 224 asymptomatic men with a median age of 36.5years. One patient (0.4%) tested positive for mpox. Ten (4.5%) and nine (4.0%) had chlamydia and gonorrhea, respectively. Our study demonstrates that screening for mpox is feasible in two Danish PrEP clinics.

Cost-effectiveness of volume computed tomography in lung cancer screening: a cohort simulation based on Nelson study outcomes

Objectives This study aimed to evaluate the cost-effectiveness of lung cancer screening (LCS) with volume-based low-dose computed tomography (CT) versus no screening for an asymptomatic high-risk population in the United Kingdom (UK), utilising the long-term insights provided by the NELSON study, the largest European randomized control trial investigating LCS. Methods A cost-effectiveness analysis was conducted using a decision tree and a state-transition Markov model to simulate the identification, diagnosis, and treatments for a lung cancer high-risk population, from a UK National Health Service (NHS) perspective. Eligible participants underwent annual volume CT screening and were compared to a cohort without the option of screening. Screen-detected lung cancers, costs, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) were predicted. Results Annual volume CT screening of 1.3 million eligible participants resulted in 96,474 more lung cancer cases detected in early stage, and 73,825 fewer cases in late stage, leading to 53,732 premature lung cancer deaths averted and 421,647 QALYs gained, compared to no screening. The ICER was £5,455 per QALY. These estimates were robust in sensitivity analyses. Limitations Lack of long-term survival data for lung cancer patients; deficiency in rigorous micro-costing studies to establish detailed treatment costs inputs for lung cancer patients. Conclusions Annual LCS with volume-based low-dose CT for a high-risk asymptomatic population is cost-effective in the UK, at a threshold of £20,000 per QALY, representing an efficient use of NHS resources with substantially improved outcomes for lung cancer patients, as well as additional societal and economic benefits for society as a whole. These findings advocate evidence-based decisions for the potential implementation of a nationwide LCS in the UK.

Improving the screening process for obstructive sleep apnea in the primary care setting.

There is a high prevalence of obstructive sleep apnea (OSA) in the primary care setting that is underdiagnosed and underreported in 75-80% of the population. If untreated, OSA has implications for long-term cardiovascular, cerebrovascular, and metabolic health. At a primary care clinic in New Jersey, patients at high risk for OSA were not being routinely screened for the condition. This project intended to address the administration of the STOP-Bang Questionnaire among asymptomatic high-risk patient populations with hypertension and/or obesity. In addition to determining each participant's level of risk for OSA, and in turn, facilitating referrals and diagnostic testing per a provider's discretion. The STOP-Bang Questionnaire, a validated screening tool for OSA, was implemented in a primary care practice to measure levels of risk for OSA among eligible participants. A total of 32 out of the 100 patients assessed were identified as high risk for OSA. After screening, 36 participants were referred for confirmatory testing. The STOP-Bang Questionnaire, a validated screening tool for OSA, is recommended for all asymptomatic high-risk patients, specifically for those with obesity and/or hypertension, at least annually. The use of a screening tool evaluates a level of risk, promotes detection of disease in the primary stages, delays disease progression, and improves treatment initiatives.

EE505 Economic Analysis of the Screening Strategy for Lung Cancer with Liquid Biopsy from a Brazilian Perspective

to perform a cost-utility analysis of a screening strategy with a liquid biopsy to detect early lung cancer detection of an asymptomatic high-risk population from the Brazilian Public Healthcare perspective.

EE304 Cost-Effectiveness of Volume Computed Tomography in Lung Cancer Screening: A Cohort Simulation Based on Nelson Study Outcomes

This study aimed to evaluate the cost-effectiveness of lung cancer screening (LCS) with volume-based low-dose computed tomography (CT) versus no screening for an asymptomatic high-risk population in the United Kingdom (UK), utilising the long-term insights provided by the NELSON study, the largest European randomized control trial investigating LCS.

Seroprevalence and burden of hepatitis C virus infection in WHO South-East Asia Region: A systematic review.

This systematic review was aimed to estimate hepatitis C virus (HCV) seroprevalence and burden in disease in WHO South East Asia Region (SEAR). Electronic databases (PubMed, Scopus, Embase, and Google Scholar) and websites of non-indexed national medical journals, government and international health agencies were searched to identify English language literature published between 1991 and June 2020. We selected the studies reporting HCV seroprevalence in asymptomatic general (low-risk) and high-risk adult populations, that is, persons living with HIV (PLHIV), persons who inject drugs (PWID), sex workers, persons on maintenance hemodialysis (MHD), people in prison, and men sex with men (MSM). Seroprevalence data were combined to estimate weighted pooled prevalence (95% confidence interval) in each group and in each country, using the random-effects model. Estimated pooled seroprevalences were multiplied with estimated populations at risk to estimate the overall HCV burden. The analysis included 538 studies (35 Bangladesh, 6 Bhutan, 2 DPR Korea, 323 India, 43 Indonesia, 2 Maldives, 18 Myanmar, 29 Nepal, 11 Sri Lanka, 67 Thailand, and 2 Timor-Leste). In SEAR, the weighted pooled anti-HCV seroprevalence was estimated as 0.84% (0.56-1.12) in low-risk population and 13.67% (10.95-16.40) in PLHIV, 51.44% (43.67-59.20) in PWID, 25.80% (20.34-32.09) in MHD, 8.39% (5.84-11.51) in prison inmates, 2.69% (1.43-4.13) in people with high-risk sex behavior, and 11.43% (8.61-14.74) in MSM. The total HCV burden in low-risk and high-risk populations in SEAR countries was estimated as 12.45 million and 1.65 million, respectively. Our estimates of HCV seroprevalence and burden should help the respective countries in planning their HCV elimination strategies.

Comprehensive Approach to Distinguish Patients with Solid Tumors from Healthy Controls by Combining Androgen Receptor Mutation p.H875Y with Cell-Free DNA Methylation and Circulating miRNAs.

Simple SummaryBlood-based tests for cancer detection are minimally invasive and could be useful for screening asymptomatic patients and high-risk populations. Since a single molecular biomarker is usually insufficient for an accurate diagnosis, we developed a multi-analyte liquid biopsy-based classification model to distinguish cancer patients from healthy subjects. The combination of cell-free DNA mutations, miRNAs, and cell-free DNA methylation markers improved the model’s performance. Moreover, we demonstrated that the androgen receptor mutation p.H875Y is not only relevant in prostate cancer but had a strong predictive value for colorectal, bladder, and breast cancer. Our results, although preliminary, showed that a single liquid biopsy test could detect multiple cancer types simultaneously.Liquid biopsy-based tests emerge progressively as an important tool for cancer diagnostics and management. Currently, researchers focus on a single biomarker type and one tumor entity. This study aimed to create a multi-analyte liquid biopsy test for the simultaneous detection of several solid cancers. For this purpose, we analyzed cell-free DNA (cfDNA) mutations and methylation, as well as circulating miRNAs (miRNAs) in plasma samples from 97 patients with cancer (20 bladder, 9 brain, 30 breast, 28 colorectal, 29 lung, 19 ovarian, 12 pancreas, 27 prostate, 23 stomach) and 15 healthy controls via real-time qPCR. Androgen receptor p.H875Y mutation (AR) was detected for the first time in bladder, lung, stomach, ovarian, brain, and pancreas cancer, all together in 51.3% of all cancer samples and in none of the healthy controls. A discriminant function model, comprising cfDNA mutations (COSM10758, COSM18561), cfDNA methylation markers (MLH1, MDR1, GATA5, SFN) and miRNAs (miR-17-5p, miR-20a-5p, miR-21-5p, miR-26a-5p, miR-27a-3p, miR-29c-3p, miR-92a-3p, miR-101-3p, miR-133a-3p, miR-148b-3p, miR-155-5p, miR-195-5p) could further classify healthy and tumor samples with 95.4% accuracy, 97.9% sensitivity, 80% specificity. This multi-analyte liquid biopsy-based test may help improve the simultaneous detection of several cancer types and underlines the importance of combining genetic and epigenetic biomarkers.

Early detection of obstructive coronary artery disease in the asymptomatic high-risk population: objectives and study design of the EARLY-SYNERGY trial

Coronary artery disease (CAD) burden for society is expected to steeply increase over the next decade. Improved feasibility and efficiency of preventive strategies is necessary to flatten the curve. Acute myocardial infarction (AMI) is the main determinant of CAD-related mortality and morbidity, and predominantly occurs in individuals with more advanced stages of CAD causing subclinical myocardial ischemia (obstructive CAD; OCAD). Unfortunately, OCAD can remain subclinical until its destructive presentation with AMI or sudden death. Current primary preventive strategies are not designed to differentiate between non-OCAD and OCAD and the opportunity is missed to treat individuals with OCAD more aggressively. EARLY-SYNERGY is a multicenter, randomized-controlled clinical trial in individuals with coronary artery calcium (CAC) presence to study (1.) the yield of cardiac magnetic resonance stress myocardial perfusion imaging (CMR-MPI) for early OCAD diagnosis and (2) whether early OCAD diagnosis improves outcomes. Individuals with CAC score ≥300 objectified in 2 population-based trials (ROBINSCA; ImaLife) are recruited for study participation. Eligible candidates are randomized 1:1 to cardiac magnetic resonance stress myocardial perfusion imaging (CMR-MPI) or no additional functional imaging. In the CMR-MPI arm, feedback on imaging results is provided to primary care provider and participant in case of guideline-based actionable findings. Participants are followed-up for clinical events, healthcare utilization and quality of life. EARLY-SYNERGY is the first randomized-controlled clinical trial designed to test the hypothesis that subclinical OCAD is widely present in the general at-risk population and that early differentiation of OCAD from non-OCAD followed by guideline-recommended treatment improves outcomes.

The Effect of Direct Health Education on the Uptake of Screening by First Degree Relatives of Glaucoma Patients in Nigeria.

First degree relatives (FDRs) of glaucoma patients are more likely to present for screening when they are directly contacted and educated by health workers on the phone compared with when they are only invited by their relative with glaucoma. The aim was to determine the effect of direct health education by phone calls on the uptake of glaucoma screening among FDRs of primary open angle glaucoma patients as a glaucoma blindness control strategy in an asymptomatic high-risk African population. This was a randomized clinical trial in which 102 primary open angle glaucoma patients (probands) were randomized into control and intervention groups. Both proband groups were educated about glaucoma and requested by the investigator to invite their adult FDR to attend a screening clinic within 1 month. In addition, the FDRs in the intervention group were directly contacted, educated, and invited for examination by phone calls. A total of 560 FDRs were enumerated by the probands. The main outcome measure was proportion of FDR that presented for screening. A total of 218 (38.9%) FDRs took up glaucoma screening services. Eighty-nine (30.1%) of the 296 FDRs in the control group and 129 (48.9%) of the 264 FDRs in the intervention group presented for examination. After multivariate analysis, FDRs in the phone call group were 2.506 times [95% confidence interval (CI): 1.695-3.706] more likely to present than FDRs in the no phone call group. Young FDRs were more likely to present [odds ratio (OR)=3.593; 95% CI: 1.613-8.007] than the elderly FDRs, while FDRs living within 200 km of the hospital were also more likely to present (OR=5.200; 95% CI: 2.860-9.456) than those living far (>200 km) away. Probands with moderate to severe visual impairment were significantly more likely (OR=3.073; 95% CI: 1.845-4.352) to have their FDRs present than probands with mild or no visual impairment. Direct contact and health education of FDRs through phone calls had a significant positive effect on the uptake of glaucoma screening by FDRs. We recommend direct contact and education of the FDRs of glaucoma patients.

Homelessness, sex and a tale of two sexually transmitted infections.

The Young People's Health Service (YPHS) is a free, nurse-led Primary Health Care Clinic, in Melbourne, for young people aged 12-24 who are experiencing homelessness. Sexually transmitted infection (STI) screening is routinely offered as part of comprehensive psychosocial assessments. We wanted to determine the number of people positive for Chlamydia trachomatis (Ct) and Mycoplasma genitalium (Mg), amongst this asymptomatic high-risk population. We also wanted to review our screening practice. All asymptomatic sexually active clients seen by YPHS between 2014 and 2016 were offered a first pass urine polymerase chain reaction-based test for Ct and Mg. Urine samples were taken for men and women. Positivity for Ct and Mg out of those tested was determined and association with gender examined. Between 2014-2016, 272 males and 278 females (n = 550) were screened for Ct, and 72 infections were detected (13.1%. Chlamydia positivity did not differ between males (n = 35; 12.9%, 95% confidence interval [CI]: 8.8-16.8) and females (n = 37; 13.3%, 95%CI: 9.3-17.3). Over the same period 273 males and 284 females were screened for Mg (n = 557) and 55 infections were detected (9.9%). A higher proportion of females (n = 35; 12.3%, 95%CI: 8.5-16.1) tested positive compared to males (n = 20; 7.3%, 95%CI: 4.2-10.4), p = 0.048. Our study demonstrates both Ct and Mg are prevalent in the population, Mg being more common in young women than young men. Referral for specialist care for macrolide-resistant Mg increased and the updated Australian STI management guidelines led to a review of practice.

Research progress of the chemoprevention agents for breast cancer

As one of the most common malignant tumors in women, breast cancer has the characteristics of high incidence, strong invasion, easy recurrence and metastasis. Although the mortality of breast cancer has decreased in recent years, its incidence has not been effectively controlled. Chemoprevention is a kind of preventive measure to reduce the incidence of disease by using natural or synthetic chemical drugs to prevent the asymptomatic high-risk population. At present, only estrogen receptor modulators and aromatase inhibitors are allowed to be used in clinical chemoprevention of breast cancer. Therefore, researcher should actively take measures to find new high-efficient, low-toxic chemoprevention agents that take into account the majority of the population. The main purpose of this review is to summarize the mechanisms and related experimental studies of six chemoprevention agents for breast cancer including estrogen receptor modulators, include aromatase inhibitors, aspirin, metformin, flavones and poly(ADP-ribose) polymerases inhibitors. Key words: Breast neoplasms; Chemoprevention; Aspirin; Flavones; Poly(ADP-ribose) polymerases

Risk stratifying asymptomatic left ventricular systolic dysfunction in the community: beyond left ventricular ejection fraction.

Midwall fractional shortening (MWFS) is a measure of left ventricular (LV) systolic function that is more reliable in case of concentric LV geometry compared to LV ejection fraction (LVEF). We hypothesized that MWFS might predict heart failure (HF) and death in a high-risk asymptomatic population, beyond other echocardiographic parameters. Among 4047 subjects aged ≥55/≤80 years followed by 10 general practitioners in northern Italy, the DAVID-Berg study prospectively enrolled 623 asymptomatic outpatients at increased risk for HF. Baseline evaluation included clinical visit, electrocardiogram, N-terminal pro-brain natriuretic peptide (NT-proBNP), and echocardiogram. Mean age of the population was 69 ± 7 years, 56% were men, 88% had hypertension, mean LVEF was 61 ± 9%, and mean MWFS 16.2 ± 3.3. During a median follow-up of 5.7 years, 95 subjects experienced HF/death events. At Cox analysis, lower MWFS was the only echocardiographic parameter, among structural/functional ones, associated with higher risk of HF/death [hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.84-0.95, Padjusted < 0.001]. The risk of HF/death related to clinical data and NT-proBNP (baseline model) was reclassified by echocardiography only when MWFS was included into the model (baseline C-statistics 0.761; adding conventional structural/functional echocardiographic data 0.776, P = 0.09; adding MWFS 0.791, P = 0.007). Compared to subjects with normal LVEF and MWFS, only subjects with combined systolic dysfunction (11% of the population) were at higher risk (P = 0.001 for both abnormal; P > 0.24 for either LVEF or MWFS abnormal). DAVID-Berg data suggest to include MWFS assessment in clinical practice, a simple and reliable echocardiographic parameter able to improve risk stratification in subjects at high risk for HF.

N-Terminal Pro B-Type Natriuretic Peptide's Usefulness for Paroxysmal Atrial Fibrillation Detection Among Populations Carrying Cardiovascular Risk Factors.

Background: Atrial fibrillation (AF) systematic screening studies have not shown a clear usefulness in stroke prevention, as AF might present as paroxysmal and asymptomatic. This study aims to determine the usefulness of some blood-biomarkers to identify paroxysmal atrial fibrillation in the context of a screening programme.Methods: A total of 100 subjects aged 65–75 years with hypertension and diabetes were randomly selected. AF was assessed by conventional electrocardiogram (ECG) and 4 weeks monitoring with a wearable Holter device (Nuubo™). N-terminal pro B-type natriuretic peptide (NT-proBNP), apolipoprotein CIII (ApoC-III), von Willebrand factor (vWF), ADAMTS13, urokinase plasminogen activator surface receptor (uPAR), and urokinase plasminogen activator (uPA) were determined in serum/plasma samples and the levels were compared depending on AF presence and mode of detection.Results: The AF prevalence in the studied population was found to be 20%. In seven subjects, AF was only detected after 1 month of Holter monitoring (hAF group). NT-proBNP levels were higher in subjects with AF compared with subjects with no AF (p < 0.0001), even when only taking into account the hAF group (p = 0.031). No significant differences were found in the other biomarkers. The NT-proBNP >95 pg/ml cut-off showed high sensitivity and specificity to detect AF (95%, 66.2%) or hAF (85.72%, 66.2%) and was found to be an independent predictor of AF and hAF in a logistic regression analysis. NT-proBNP correlated with AF burden (r = 0.597, p = 0.024).Conclusion: NT-proBNP was elevated in AF cases not identified by ECG; thus, it may be used as a screening biomarker in asymptomatic high-risk populations, with a promising cut-off point of 95 pg/ml that requires further validation.

Cardioembolic Ischemic Stroke Gene Expression Fingerprint in Blood: a Systematic Review and Verification Analysis.

An accurate etiological classification is key to optimize secondary prevention after ischemic stroke, but the cause remains undetermined in one third of patients. Several studies pointed out the usefulness of circulating gene expression markers to discriminate cardioembolic (CE) strokes, mainly due to atrial fibrillation (AF), while only exploring them in small cohorts. A systematic review of studies analyzing high-throughput gene expression in blood samples to discriminate CE strokes was performed. Significantly dysregulated genes were considered as candidates, and a selection of them was validated by RT-qPCR in 100 patients with defined CE or atherothrombotic (LAA) stroke etiology. Longitudinal performance was evaluated in 12 patients at three time points. Their usefulness as biomarkers for AF was tested in 120 cryptogenic strokes and 100 individuals at high-risk for stroke. Three published studies plus three unpublished datasets were considered for candidate selection. Sixty-seven genes were found dysregulated in CE strokes. CREM, PELI1, and ZAK were verified to be up-regulated in CE vs LAA (p = 0.010, p = 0.003, p < 0.001, respectively), without changes in their expression within the first 24h after stroke onset. The combined up-regulation of these three biomarkers increased the probability of suffering from CE stroke by 23-fold. In cryptogenic strokes with subsequent AF detection, PELI1 and CREM showed overexpression (p = 0.017, p = 0.059, respectively), whereas in high-risk asymptomatic populations, all three genes showed potential to detect AF (p = 0.007, p = 0.007, p = 0.015). The proved discriminatory capacity of these gene expression markers to detect cardioembolism even in cryptogenic strokes and asymptomatic high-risk populations might bring up their use as biomarkers.

Clinical Risk Factors of Asymptomatic Deep Venous Thrombosis in Patients With Acute Stroke

Background:Deep venous thrombosis (DVT) is a common complication after stroke. It is easy to identify the patients with symptomatic DVT; however, the tool for asymptomatic high-risk population needs to be further explored. Our aim was to explore the risk factors of acute stroke patients with asymptomatic DVT.Methods:We performed a prospective observation study among 452 patients with acute stroke who had a stroke within 14 days. Ultrasound examination of deep veins was repeatedly performed in each patient for DVT every 7 days during his admission. The dynamic rate of DVT in acute stroke was analyzed. Then risk factors were compared between DVT patients and non-DVT patients. The predictive model was explored based on thr cox proportion model.Results:Asymptomatic DVT was detected in 52 (11.5%) patients with stroke and 85.9% of thrombi were identified in their distal veins. Patients with longer length of stay (P = .004), more severe stroke (P = 0.001), higher level of D-dimer (P = .003), and higher blood glucose level were associated with higher risk of DVT, while patients with higher triglyceride level (P = .003) were less likely to have DVT, after adjusting age and sex. With the median of D-dimer (0.38 FEU mg/L) as cutoff value. Patients with higher level of D-dimer might have a higher risk of DVT with a significant statistical difference. Also, the severity of stroke differed DVT risk in Kaplan-Meier model. Using cox-proportion hazard regression model, asymptomatic DVT could be predicted (area under the curve 0.852).Conclusion:Our data showed that asymptomatic DVT was common in patients with acute stroke and most of thrombosis occurred in distal veins. Combination of clinical manifestation and laboratory results might be helpful predict DVT. DVT prophylaxis should be condisdered in high risk.

545: Quantitative fFN for prediction of spontaneous PTB in a high-risk asymptomatic population: the equate trial

545: Quantitative fFN for prediction of spontaneous PTB in a high-risk asymptomatic population: the equate trial

Asymptomatic polyvascular disease and the risks of cardiovascular events and all-cause death

Background and aimsAtherosclerosis is a diffuse and systemic disease. We aimed to assess prevalence and outcome of extracoronary polyvascular disease (polyVD) in the asymptomatic Chinese community population. MethodsA random sample of 5440 participants aged 40 years or older were enrolled in the Asymptomatic Polyvascular Abnormalities Community Study from 2010 to 2011. Intracranial artery stenosis, extracranial artery stenosis, and lower extremity artery disease were detected by transcranial Doppler and duplex sonography, and by calculating the ankle brachial index. The study endpoints included the first occurrence of stroke, myocardial infarction (MI) and all-cause death. ResultsPolyVD (two or three affected vascular territories) was found in 3.0% of the participants, and was significantly higher in men (4.3%). Over a median follow-up of 4.1 years, we identified a total of 247 events (4.7%), including 83 strokes (68 ischemic), 45 MIs and 134 all-cause deaths. After adjusting for age, gender and other potential confounders, we found a significant increase in risk of major cardiovascular events as well as all-cause death in participants with polyVD. In multivariate Cox regression analyses, the adjusted hazard ratios (HR) (95% confidence interval, CI) for the composite of stroke, MI and all-cause death for single and poly-vascular disease (compared with 0 vascular disease) increased from 1.58 (1.19–2.12) to 1.95 (1.26–3.03). Similarly, the adjusted HR (95% CI) for all-cause death for single and poly-vascular disease increased from 1.53 (1.03–2.29) to 2.22 (1.27–3.86). ConclusionsPolyVD significantly increased the risk of major cardiovascular events and all-cause death in the asymptomatic community population. Performing invasive screening tests for polyVD is useful in the high-risk asymptomatic population.

Abstract 17265: The Relationship Between Subclinical Coronary Artery Atheroscelrosis and Brain Ischemic White Matter Disease in Healthy Individuals from High Risk Families

Background: Ischemic white matter disease (IWMD) is associated with incident stroke. Similarly subclinical coronary artery disease is associated with incident coronary artery disease (CAD) events. Although, atherogenesis in both vascular beds likely shares common mechanisms, the extent to which subclinical CAD is associated with preclinical IWMD in a young to middle-aged healthy asymptomatic high risk population with a family history of premature CAD remains unknown. Methods: We screened 405 apparently healthy participants in Genetic Study of Atherosclerotic Risk (GeneSTAR) (mean age 51.6 ± 10.6 years, 60% female, 36% African American) for CAD risk factors, and for the presence of calcified and noncalcified coronary plaque using dual-source 256 multi-detector cardiac CT angiography. The presence of IWMD was assessed by 3 Tesla brain MRI and the ischemic white-matter volume to brain volume (WVBV) ratio was calculated using direct measurements. A multivariate linear regression analysis predicting WVBV was performed for the presence of CAD, adjusting for age, sex, race, traditional CAD risk factors, and intrafamilial correlations using a generalized estimating equation (GEE). Results: Subclinical CAD was highly prevalent (43.0%). Individuals with coronary plaque had a higher ratio of WVBV (median 0.11, interquartile range [0.04 to 0.33]) as compared to those without coronary plaque (median 0.05 [0.01 to 0.14], p&lt;0.001). In the fully adjusted analysis, the presence of subclinical CAD was a significant predictor of WVBV (p=0.05), as was age (p&lt;0.001). Conclusion: This is the first study to show a strong association of subclinical CAD and occult ischemic white mater disease in healthy high-risk young to middle aged individuals, independent of traditional CAD risk factors, including age. The findings support the premise of shared causal pathways in the two vascular beds in families at increased risk for both CAD and stroke.