Measures Of Subclinical Disease Research Articles

Assessment of Subclinical Atherosclerosis in Asymptomatic People In Vivo: Measurements Suitable for Biomarker and Mendelian Randomization Studies.

One strategy to reduce the burden of cardiovascular disease is the early detection and treatment of atherosclerosis. This has led to significant interest in studies of subclinical atherosclerosis, using different phenotypes, not all of which are accurate reflections of the presence of asymptomatic atherosclerotic plaques. The aim of part 2 of this series is to provide a review of the existing literature on purported measures of subclinical disease and recommendations concerning which tests may be appropriate in the prevention of incident cardiovascular disease. We conducted a critical review of measurements used to infer the presence of subclinical atherosclerosis in the major conduit arteries and focused on the predictive value of these tests for future cardiovascular events, independent of conventional cardiovascular risk factors, in asymptomatic people. The emphasis was on studies with >10 000 person-years of follow-up, with meta-analysis of results reporting adjusted hazard ratios (HRs) with 95% CIs. The arterial territories were limited to carotid, coronary, aorta, and lower limb arteries. In the carotid arteries, the presence of plaque (8 studies) was independently associated with future stroke (pooled HR, 1.89 [1.04-3.44]) and cardiac events (7 studies), with a pooled HR, 1.77 (1.19-2.62). Increased coronary artery calcium (5 studies) was associated with the risk of coronary heart disease events, pooled HR, 1.54 (1.07-2.07) and increasing severity of calcification (by Agaston score) was associated with escalation of risk (13 studies). An ankle/brachial index (ABI) of <0.9, the pooled HR for cardiovascular death from 7 studies was 2.01 (1.43-2.81). There were insufficient studies of either, thoracic or aortic calcium, aortic diameter, or femoral plaque to synthesize the data based on consistent reporting of these measures. The presence of carotid plaque, coronary artery calcium, or abnormal ankle pressures seems to be a valid indicator of the presence of subclinical atherosclerosis and may be considered for use in biomarker, Mendelian randomization and similar studies.

The association between leptin and subclinical cardiovascular disease explained by body fat: Observational and Mendelian randomization analyses

Background and aimsLeptin has been associated with adverse effects on cardiovascular disease, but the effect of confounding by body fat in these associations remains unclear. To investigate associations between leptin and heart function and subclinical cardiovascular disease adjusted for total body fat, and to investigate the causal relation between leptin and cardiovascular disease using Mendelian randomisation. Methods and resultsLeptin concentrations, total body fat and diverse measures of subclinical cardiovascular disease were determined in participants of the Netherlands Epidemiology of Obesity study. Linear regression between leptin concentration and measures of heart function, ECG measures, and carotid intima media thickness as a measure of subclinical atherosclerosis was adjusted for potential confounding factors, and additionally including total body fat. We analysed the combined effects of genetic variants from a GWAS on leptin concentrations in publicly-available summary statistics of coronary heart disease GWAS (CARDIoGRAMplusC4D, n = 184,305). As many as 6107 men and women, mean (SD) age 56 (6) years, BMI 26 (4) kg/m2, and median leptin concentration 12.1 μg (IQR: 6.7–22.6) were included.In observational analyses, leptin was weakly associated with heart function and subclinical cardiovascular disease, but these associations attenuated when adjusting for total body fat. A doubling of genetically-determined leptin concentration was associated with an odds ratio of cardiovascular disease of 0.69 (0.37, 1.27). ConclusionObservational associations between leptin and subclinical measures of cardiovascular disease were largely explained by differences in total body fat. Results of analyses of genetically-determined leptin and coronary heart disease risk were inconclusive due to a large confidence interval.

NEIGHBORHOOD QUALITY AS IT RELATES TO HEALTH AND WELL-BEING IN OLDER AFRICAN AMERICANS

Abstract With the burgeoning older adult population, there will be an increased demand for neighborhood environments that are conducive to successful aging. For example, the need for affordable and usable housing developments for older adults that provide greater opportunities for social engagement, social services, and convenience to neighborhood resources (e.g., grocery stores, healthcare) will continue to rise. Several initiatives have sought to develop age-friendly neighborhoods, which focused on improving accessibility and affordability of community resources. However, limited effort has focused on the health and cognitive effects of neighborhood-level socioeconomic disadvantage, with respect to neighborhood income, education, employment, and housing quality. This symposium will include presentations from two studies that explored how neighborhood disadvantage (measured by the Area Deprivation Index) relates to health and cognition. The objectives of the proposed symposium are the following: (1) discuss how neighborhood disadvantage relates to subjective and objective measures of physical health; and (2) discuss how neighborhood disadvantage relates to cognitive functioning. Allan and colleagues explored the association between neighborhood disadvantage as it relates to changes in self-reported health and objective measures (i.e., blood pressure) of health among older Black adults. Wright and colleagues explored the association between neighborhood disadvantage and measures of subclinical cardiovascular disease in older Black and White adults. Aiken-Morgan and colleagues examined associations between neighborhood disadvantage and cognitive functioning among Black older adults. Lastly, McCain and colleagues explored associations between neighborhood disadvantage and mobility among Black older adults.

Subclinical hepatic fibrosis is associated with coronary microvascular dysfunction by myocardial perfusion reserve index: a retrospective cohort study.

The heart-liver axis is of growing importance. Previous studies have identified independent association of liver dysfunction and fibrosis with adverse cardiac outcomes, but mechanistic pathways remain uncertain. We sought to understand the relations between the degree of hepatic fibrosis identified by the Fibrosis-4 (Fib-4) risk score and comprehensive cardiac MRI (CMR) measures of subclinical cardiac disease. We conducted a retrospective single-center cohort study of patients between 2011 and 2021. We identified consecutive patients who underwent a comprehensive CMR imaging protocol including contrast enhanced with stress/rest perfusion, and lacked pre-existing cardiovascular disease or perfusion abnormalities on CMR. We examined the association of hepatic fibrosis, using the Fib-4 score, with subclinical cardiac disease on CMR while adjusting for cardiometabolic traits. Given known associations of hepatic disease and coronary microvascular dysfunction, we prioritized analyses with the myocardial perfusion reserve index (MPRI), a marker of coronary microvascular function. Of the 66 patients in our study cohort, 54 were female (81%) and the mean age was 53.7 ± 15.3years. We found that higher Fib-4 was associated with reduction in the MPRI (β [SE] - 1.12 [0.46], P = 0.02), after adjusting for cardiometabolic risk factors. Importantly, Fib-4 was not significantly associated with any other CMR phenotypes including measures of cardiac remodeling, inflammation, fibrosis, or dysfunction. We found evidence that hepatic fibrosis associated with coronary microvascular dysfunction, in the absence of overt associations with any other subclinical cardiac disease measures. These findings highlight a potentially important precursor pathway leading to development of subsequent heart-liver disease.

Heightened splenic and bone marrow uptake of 18F-FDG PET/CT is associated with systemic inflammation and subclinical atherosclerosis by CCTA in psoriasis: An observational study

Background and aimsPsoriasis is an immune-mediated inflammatory disease with increased risk of myocardial infarction. Preclinical studies in psoriasis models show an association between chronic inflammation and immune cell proliferation in the spleen and bone marrow (BM). We sought to test the hypothesis that splenic and BM 18F-fluorodeoxyglucose (18F-FDG) uptake is heightened in psoriasis and that higher uptake associates with systemic inflammation and subclinical atherosclerotic disease measures in this cohort. MethodsMultimodality imaging and biomarker assays were performed in 240 participants (210 with psoriasis and 30 healthy). Splenic and BM uptake was obtained using 18F-FDG positron emission tomography/computed tomography (PET/CT). Coronary artery plaque characteristics including non-calcified burden (NCB) and lipid rich necrotic core (LRNC) were quantified using a dedicated software for CT angiography. All analyses were performed with StataIC 16 (Stata Corp., College Station, TX, USA). ResultsSplenic and BM 18F-FDG uptake was increased in psoriasis (vs. healthy volunteers) and significantly associated with proatherogenic lipids, immune cells and systemic inflammation. Higher splenic 18F-FDG uptake associated with higher total coronary burden (β = 0.37; p<0.001), NCB (β = 0.39; p<0.001), and LRNC (β = 0.32; p<0.001) in fully adjusted models. Similar associations were seen for BM 18F-FDG uptake in adjusted models (β = 0.38; β = 0.41; β = 0.24; respectively, all p<0.001). ConclusionsHeightened splenic and BM uptake of 18F-FDG is associated with proatherogenic lipids, immune cells, inflammatory markers and coronary artery disease. These findings provide insights into atherogenic mechanisms in psoriasis and suggest that immune cell proliferation in the spleen and BM is associated with subclinical atherosclerosis.

Abstract 009: Incremental Predictive Utility Of Subclinical Disease Measures For Cardiovascular Disease Risk

Introduction: The Framingham Risk Score (FRS) has been widely used to predict cardiovascular disease (CVD) risk. However, a comparison of the incremental prognostic utility of different subclinical disease (SubDz) measures is not clear. Methods: We evaluated participants aged 40-79 years (mean age 55 years, 56% women) from the Framingham Offspring (Exam 8, 2005-2008) and Third Generation cohorts (Exam 1, 2002-2005), free of CVD and diabetes, with data on coronary artery calcium (CAC, n=2497), and two measures of target organ damage: urine albumin-to-creatinine ratio (UACR, n=4011) and left ventricular mass (LVM, n=3770). We categorized FRS: &lt;10%, 10-19%, and ≥20% and defined high CAC as CAC≥100, microalbuminuria (MA) as UACR ≥25mg/g in men and ≥35mg/g in women, and left ventricular hypertrophy (LVH) as LVM/body surface area&gt;115 g/m 2 (men) and &gt;95g/m 2 (women). We created 6 cross-classified groups: FRS &lt;10%-No SubDz; FRS &lt;10% + SubDz; FRS 10-19%-No SubDz; FRS 10-19% + SubDz; FRS ≥20%-No SubDz; and FRS ≥20% + SubDz. We related the groups to CVD risk using Cox regression adjusting for age, sex, and cohort and plotted Kaplan-Meier curves to display CVD cumulative incidence by each SubDz cross-classified group. Results: Over a median follow-up of 12 years, 7% of participants developed CVD. Comparing FRS 10-19%-No SubDz and FRS 10-19% + SubDz to FRS &lt;10%-No SubDz (referent), we observed hazards ratios (95% CI) for CVD of 1.68 (0.99-2.83) and 6.50 (3.64-11.61) for high CAC; 1.33 (0.95-1.85) and 2.15 (1.10-4.18) for MA; and 1.43 (0.99-2.07) and 2.18 (1.33-3.57) for LVH. Each SubDz measure predicted CVD risk incrementally over the FRS. In a sub-sample with all three SubDz measures, the model c-statistic with FRS only was 0.725, increasing to 0.773, 0.726, and 0.728 when adding CAC, MA, and LVH, respectively. Conclusion: Presence of a high CAC score outperformed other measures of target organ damage (MA or LVH) for predicting CVD risk, regardless of FRS. Additional studies of larger multi-ethnic samples are warranted to confirm our findings.

Abstract P133: Circulating Anti-Müllerian Hormone and Subclinical Cardiovascular Disease in Middle-aged and Older Men

Introduction: Anti-Müllerian hormone (AMH) is primarily known for its role in sexual differentiation during embryogenesis, and ovarian follicle development in premenopausal women. Furthermore, recent research suggests that higher AMH levels are associated with a lower occurrence of (subclinical) cardiovascular disease (CVD) in both women and men. However, these studies only included a small variety of subclinical CVD measures. We aimed to investigate whether circulating AMH is associated with a wider range of subclinical CVD measures in middle-aged and older men. Hypothesis: Higher AMH levels are associated with more favorable levels of subclinical CVD measures. Methods: We analyzed data from 371 male participants (aged 40-80 years at recruitment) from a Dutch population-based study. AMH was measured in serum samples obtained at recruitment using the Elecsys ® AMH assay (Roche Diagnostics). At baseline we measured carotid intima-media thickness (cIMT)(μm), pulse wave velocity (PWV)(m/s) and aorta diameter (cm), and calculated Framingham risk score predictions. We investigated associations between AMH (μg/L) levels, both continuously and in tertiles, and these outcomes using linear regression models adjusted for known CVD risk factors, free testosterone, free estradiol and dihydroepiandrosterone sulphate (DHEAS). Sensitivity analyses comprised exclusion of prevalent diabetes and CVD cases. Results: Higher AMH levels were associated with a lower cIMT at baseline (β continuousAMH = -6.3, 95%CI: -10.7, -1.9; β T2vsT1 = -30.6, 95%CI: -60.2, -0.9; β T3vsT1 = -39.8, 95%CI: -70.1, -9.6). We observed no statistically significant associations between AMH and the remaining outcomes, but effect estimates indicated that higher AMH levels may be associated with lower PWV (β continuousAMH = -0.02, 95%CI: -0.10, 0.05), and lower Framingham risk score predictions (β continuousAMH = -0.004, 95%CI: -0.008, 0.000). Exclusion of prevalent diabetes and CVD cases did not change our conclusions. Conclusions: The results of this study suggest that higher AMH levels are associated with a lower cIMT in middle-aged and older men. Based on our results we cannot exclude a possible relation between circulating AMH levels and other measures of subclinical cardiovascular disease.

Comparisons of the Framingham and Pooled Cohort Equation Risk Scores for Detecting Subclinical Vascular Disease in Blacks Versus Whites

The pooled cohort Atherosclerotic Cardiovascular Disease (ASCVD) risk calculator is designed to improve cardiovascular risk estimation compared with the Framingham Risk Score, particularly in blacks. Although the ASCVD risk score better predicts mortality and incident cardiovascular disease in blacks, less is known about its performance for subclinical vascular disease measures, including arterial stiffness and carotid intima-media thickness. We sought to determine if the ASCVD risk score better identifies subclinical vascular disease in blacks compared with the Framingham risk score. We calculated both the Framingham and ASCVD cohort risk scores in 1,231 subjects (mean age 53 years, 59% female, 37% black) without known cardiovascular disease and measured the extent of arterial stiffness, as determined by pulse wave velocity (PWV), central pulse pressure (CPP), and central augmentation index (CAIx), and subclinical atherosclerosis, as determined by carotid-IMT (C-IMT). Compared with whites, blacks had higher CAIx (23.9 ± 10.2 vs 22.1 ± 9.6%, p = 0.004), CPP (36.4 ± 10.5 vs 34.9 ± 9.8 mmHg, p = 0.014), PWV (7.6 ± 1.5 vs 7.3 ± 1.3 m/s, p = 0.004), and C-IMT (0.67 ± 0.10 vs 0.65 ± 0.10 mm, p = 0.005). In a multivariable analysis including race and Framingham risk score, race remained an independent predictor of all measures of subclinical vascular disease; however, models with race and the ASCVD risk score showed that race was not an independent predictor of subclinical vascular disease. In conclusion, greater subclinical vascular disease in blacks was not estimated by the Framingham risk score. The new ASCVD risk score provided a better estimate of racial differences in vascular function and structure.

Brief Report: Physical Activity, Body Mass Index and Arterial Stiffness in Children with Autism Spectrum Disorder: Preliminary Findings.

We examined the association between physical activity (PA), body mass index (BMI) and novel measures of subclinical cardiovascular disease (CVD) in 15 children with autism spectrum disorder (ASD) (mean age 7 ± 2 years, 2 girls). PA was objectively assessed using accelerometry as time spent in moderate-vigorous physical activity (MVPA). Arterial stiffness was measured via aortic pulse wave velocity (PWV) and taken as a marker of subclinical CVD risk. MVPA was inversely associated with aortic PWV (r = - 0.46, p < 0.05). BMI percentile was positively associated with aortic PWV (r = 0.61, p < 0.05). Overall findings suggest that reduced PA and higher body mass in children with ASD are associated with increased arterial stiffness which may have a detrimental impact on overall cardiovascular health.

EGFR and Albuminuria in Relation to Risk of Incident Atrial Fibrillation: A Meta-Analysis of the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health Study.

The incidence of atrial fibrillation is high in ESRD, but limited data are available on the incidence of atrial fibrillation across a broad range of kidney function. Thus, we examined the association of eGFR and urine albumin-to-creatinine ratio with risk of incident atrial fibrillation. We meta-analyzed three prospective cohorts: the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health Study. Cox regression models were performed examining the association of eGFR and urine albumin-to-creatinine ratio with incident atrial fibrillation adjusting for demographics and comorbidity. In additional analyses, we adjusted for measures of subclinical cardiovascular disease (by electrocardiogram and cardiac imaging) and interim heart failure and myocardial infarction events. In the meta-analyzed study population of 16,769 participants without prevalent atrial fibrillation, across categories of decreasing eGFR (eGFR>90 [reference], 60-89, 45-59, 30-44, and <30 ml/min per 1.73 m2), there was a stepwise increase in the adjusted risk of incident atrial fibrillation: hazard ratios (95% confidence intervals) were 1.00, 1.09 (0.97 to 1.24), 1.17 (1.00 to 1.38), 1.59 (1.28 to 1.98), and 2.03 (1.40 to 2.96), respectively. There was a stepwise increase in the adjusted risk of incident atrial fibrillation across categories of increasing urine albumin-to-creatinine ratio (urine albumin-to-creatinine ratio <15 [reference], 15-29, 30-299, and ≥300 mg/g): hazard ratios (95% confidence intervals) were 1.00, 1.04 (0.83 to 1.30), 1.47 (1.20 to 1.79), and 1.76 (1.18 to 2.62), respectively. The associations were consistent after adjustment for subclinical cardiovascular disease measures and interim heart failure and myocardial infarction events. In this meta-analysis of three cohorts, reduced eGFR and elevated urine albumin-to-creatinine ratio were significantly associated with greater risk of incident atrial fibrillation, highlighting the need for further studies to understand mechanisms linking kidney disease with atrial fibrillation.

P4406The associations of overall and abdominal adiposity with ECG measures of subclinical cardiovascular disease in a middle-aged population

P4406The associations of overall and abdominal adiposity with ECG measures of subclinical cardiovascular disease in a middle-aged population

Association of Cardiovascular Health With Subclinical Disease and Incident Events: The Multi-Ethnic Study of Atherosclerosis.

BackgroundFew adults have ideal cardiovascular health (CVH). We studied associations of an overall CVH score with subclinical cardiovascular disease and events. We assessed whether associations varied by race/ethnicity.Methods and ResultsAmong 5961 participants in the Multi‐Ethnic Study of Atherosclerosis, components of CVH were measured at baseline, 2000‐2002: systolic blood pressure, total cholesterol, fasting glucose, smoking, physical activity, diet, and body mass index. Levels were classified as ideal (2 points), intermediate (1 point), and poor (0 points) according to American Heart Association definitions. Points were summed to produce a CVH score (0‐7 low, 8‐11 moderate, 12‐14 high). Coronary artery calcium, carotid intima‐media thickness, and left ventricular mass were measured at baseline. Cardiovascular disease was defined as myocardial infarction, coronary heart disease death, resuscitated cardiac arrest, stroke, heart failure, or peripheral artery disease. Follow‐up was 10.3 years. Regression models were used to examine associations of the CVH score with subclinical disease and events, adjusting for age, sex, and education. Analyses were stratified by race/ethnicity. Adults with high or moderate CVH scores had significantly lower odds of coronary artery calcium and lower carotid intima‐media thickness and left ventricular mass than adults with low CVH scores. Adults with high or moderate CVH scores were 67% (95%CI 41% to 82%) and 37% (95%CI 22% to 49%) less likely, respectively, to experience a cardiovascular disease event than adults with low scores. There was no interaction with race/ethnicity.ConclusionsThere is a graded inverse association between CVH scores and measures of subclinical and overt cardiovascular disease that is similar across race/ethnic groups.

Providing Evidence for Subclinical CVD in Risk Assessment.

When the MESA (Multi-Ethnic Study of Atherosclerosis) began, the Framingham risk score was the preferred tool for 10-year global coronary heart disease risk assessment; however, the Framingham risk score had limitations including derivation in a homogenous population lacking racial and ethnic diversity and exclusive reliance on traditional risk factors without consideration of most subclinical disease measures. MESA was designed to study the prognostic value of subclinical atherosclerosis and other risk markers in a multiethnic population. In a series of landmark publications, MESA demonstrated that measures of subclinical cardiovascular disease add significant prognostic value to the traditional Framingham risk variables. In head-to-head studies comparing these markers, MESA established that the coronary artery calcium score may be the single best predictor of coronary heart disease risk. Results from MESA have directly influenced recent prevention guidelines including the recommendations on risk assessment and cholesterol-lowering therapy. The MESA study has published its own risk score, which allows for the calculation of 10-year risk of coronary heart disease before and after knowledge of a coronary artery calcium score.

Peripheral Artery Disease and Aortic Disease.

We reviewed published MESA (Multi-Ethnic Study of Atherosclerosis) study articles concerning peripheral arterial disease, subclavian stenosis (SS), abdominal aortic calcium (AAC), and thoracic artery calcium (TAC). Important findings include, compared to non-Hispanic whites, lower ankle-brachial index (ABI) and more SS in African Americans, and higher ABI and less SS in Hispanic and Chinese Americans. Abnormal ABI and brachial pressure differences were associated with other subclinical cardiovascular disease (CVD) measures. Both very high and low ABI independently predicted increased CVD events. Looking at aortic measures, TAC and AAC were significantly associated with other subclinical CVD measures. Comparisons of AAC with coronary artery calcium (CAC) showed that both were less common in ethnic minority groups. However, although CAC was much more common in men than in women in multivariable analysis, this was not true of AAC. Also, when AAC and CAC were adjusted for each other in multivariable analysis, there was a stronger association for AAC than for CAC with CVD and total mortality.

Life Course Socioeconomic Position and Subclinical Disease: The Jackson Heart Study.

African Americans experience higher rates of cardiovascular disease (CVD) and lower childhood and adult socioeconomic position (SEP). Research that examines the associations of multiple measures of SEP with subclinical CVD markers among African Americans is limited. Data from the Jackson Heart Study (JHS) were used to examine cross-sectional associations of childhood SEP and adult SEP with subclinical markers among 4,756 African American participants (mean age 54, 64% female), adjusting for age, health behaviors and CVD risk factors. Subclinical markers included prevalent left ventricular hypertrophy (LVH), peripheral artery disease (PAD), coronary artery calcification (CAC), and carotid intima-media thickness (CIMT). The prevalence of LVH, PAD and CAC was 7%, 6% and 45%, respectively. The mean CIMT was .72 ± .17 mm. In fully-adjusted models, having a college education was inversely associated with PAD (OR, .27; 95% CI .13,.56) and CIMT (β=-29.7, P<.01). Income was inversely associated with LVH after adjustment for health behaviors (OR, .49 95% CI .25,.96), though associations attenuated in the fully-adjusted model. Measures of childhood SEP (material resources and mother's education) were not consistently associated with subclinical disease measures other than a positive association between material resources and CIMT. Subclinical disease markers were patterned by adult SEP measures among African Americans.

Low-glycaemic index diet to improve glycaemic control and cardiovascular disease in type 2 diabetes: design and methods for a randomised, controlled, clinical trial

IntroductionType 2 diabetes (T2DM) produces macrovascular and microvascular damage, significantly increasing the risk of cardiovascular disease (CVD), renal failure and blindness. As rates of T2DM rise, the need for effective...

Development and Validation of Risk Prediction Models for Cardiovascular Events in Black Adults: The Jackson Heart Study Cohort.

Cardiovascular risk assessment is a fundamental component of prevention of cardiovascular disease (CVD). However, commonly used prediction models have been formulated in primarily or exclusively white populations. Whether risk assessment in black adults is dissimilar to that in white adults is uncertain. To develop and validate risk prediction models for CVD incidence in black adults, incorporating standard risk factors, biomarkers, and subclinical disease. The Jackson Heart Study (JHS), a longitudinal community-based study of 5301 black adults in Jackson, Mississippi. Inclusive study dates were the date of a participant's first visit (September 2000 to March 2004) to December 31, 2011. The median (75th percentile) follow-up was 9.1 (9.7) years. The dates of the analysis were August 2013 to May 2015. Measurements included standard risk factors, including age, sex, body mass index, systolic and diastolic blood pressure, ratio of fasting total cholesterol to high-density lipoprotein cholesterol, estimated glomerular filtration rate, antihypertensive therapy, diabetes mellitus, and smoking; blood biomarkers; and subclinical disease measures, including ankle-brachial index, carotid intimal-medial thickness, and echocardiographic left ventricular hypertrophy and systolic dysfunction. Incident CVD event was defined as the first occurrence of myocardial infarction, coronary heart disease death, congestive heart failure, stroke, incident angina, or intermittent claudication. Model performance was compared with the American College of Cardiology/American Heart Association (ACC/AHA) CVD risk algorithm and the Framingham Risk Score (FHS) refitted to the JHS data and evaluated in the Atherosclerosis Risk in Communities (ARIC) and Multi-Ethnic Study of Atherosclerosis cohorts. The study cohort comprised 3689 participants with mean (SD) age at baseline was 53 (11) years, and 64.8% (n = 2390) were female. Over a median of 9.1 years, 270 participants (166 women) experienced a first CVD event. A simple combination of standard CVD risk factors, B-type natriuretic peptide, and ankle-brachial index (model 6) yielded modest improvement over a model without B-type natriuretic peptide and ankle-brachial index (C statistic, 0.79; 95% CI, 0.75-0.83 [relative integrated discrimination improvement, 0.22; 95% CI, 0.15-0.30]). However, the reclassification improvement was not substantially different between model 6 and the ACC/AHA CVD Pooled Cohort risk equations or between model 6 and the FHS. The models discriminated reasonably well in the ARIC and Multi-Ethnic Study of Atherosclerosis data (C statistic range, 0.70-0.77). Our findings using the JHS data in the present study are valuable because they confirm that current FHS and ACC/AHA risk algorithms work well in black individuals and are not easily improved on. A unique risk calculator for black adults may not be necessary.

Subclinical Cardiovascular Disease and Death, Dementia, and Coronary Heart Disease in Patients 80+ Years

BackgroundThe successful prevention and treatment of coronary heart disease (CHD) and stroke has resulted in a substantial increase in longevity, with subsequent growth in the population of older people at risk for dementia. ObjectivesThe authors evaluated the relationship of coronary and other peripheral atherosclerosis to risk of death, dementia, and CHD in the very elderly. Because the extent of vascular disease differs substantially between men and women, sex- and race-specific analyses were included, with a specific focus on women with low coronary artery calcium (CAC) Agatston scores. MethodsWe evaluated the relationship between measures of subclinical cardiovascular disease (CAC, carotid intimal medial thickness, stenosis, and ankle brachial index) and risk of dementia, CHD, and total mortality in 532 participants of the Cardiovascular Health Study-Cognition Study from 1998/1999 (mean age, 80 years) to 2012/2013 (mean age, 93 years). ResultsThirty-six percent of participants had CAC scores >400. Women and African-Americans had lower CAC scores. Few men had low CAC scores. CAC score and number of coronary calcifications were directly related to age-adjusted total mortality and CHD. The age-specific incidence of dementia was higher than for CHD. Only about 25% of deaths were caused by CHD and 16% by dementia. Approximately 64% of those who died had a prior diagnosis of dementia. White women with low CAC scores had a significantly decreased incidence of dementia. ConclusionsIn subjects 80+ years of age, there is a greater incidence of dementia than of CHD. CAC, as a marker of atherosclerosis, is a determinant of mortality, and risk of CHD and myocardial infarction. White women with low CAC scores had a significantly decreased risk of dementia. A very important unanswered question, especially in the very elderly, is whether prevention of atherosclerosis and its complications is associated with less Alzheimer disease pathology and dementia. (Cardiovascular Health Study [CHS]; NCT00005133)

Association of Exhaled Carbon Monoxide With Stroke Incidence and Subclinical Vascular Brain Injury: Framingham Heart Study.

Exhaled carbon monoxide (CO) is associated with cardiometabolic traits, subclinical atherosclerosis, and cardiovascular disease, but its specific relations with stroke are unexplored. We related exhaled CO to magnetic resonance imaging measures of subclinical cerebrovascular disease cross-sectionally and to incident stroke/transient ischemic attack prospectively in the Framingham Offspring study. We measured exhaled CO in 3313 participants (age 59±10 years; 53% women), and brain magnetic resonance imaging was available in 1982 individuals (age 58±10 years; 54% women). Participants were analyzed according to tertiles of exhaled CO concentration. In age- and sex-adjusted models, the highest tertile of exhaled CO was associated with lower total cerebral brain volumes, higher white-matter hyperintensity volumes, and greater prevalence of silent cerebral infarcts (P<0.05 for all). The results for total cerebral brain volume and white-matter hyperintensity volume were consistent after removing smokers from the sample, and the association with white-matter hyperintensity volume persisted after multivariable adjustment (P=0.04). In prospective analyses (mean follow-up 12.9 years), higher exhaled CO was associated with 67% (second tertile) and 97% (top tertile) increased incidence of stroke/transient ischemic attack relative to the first tertile that served as referent (P<0.01 for both). These results were consistent in nonsmokers and were partially attenuated upon adjustment for vascular risk factors. In this large, community-based sample of individuals without clinical stroke/transient ischemic attack at baseline, higher exhaled CO was associated with a greater burden of subclinical cerebrovascular disease cross-sectionally and with increased risk of stroke/transient ischemic attack prospectively. Further investigation is necessary to explore the biological mechanisms linking elevated CO with stroke.

Abstract 16816: Association of Exhaled Carbon Monoxide With Stroke Incidence and Subclinical Vascular Brain Injury: The Framingham Study

Introduction: Exhaled carbon monoxide (CO) is associated with cardiometabolic traits, subclinical atherosclerosis, and cardiovascular disease, but its specific relations with stroke have not been explored. Hypothesis: We hypothesized that exhaled CO is related to MRI measures of subclinical cerebrovascular disease cross-sectionally, and to incident stroke/ transient ischemic attack (TIA) prospectively in the Framingham Offspring Study. Methods: We measured exhaled CO in 3313 participants (age 59±10 years, 53% women) and Brain MRI imaging was available in 1982 individuals (age 58±10, 54% women). Participants were analyzed according to tertiles of exhaled CO concentration. Results: In age- and sex-adjusted models, the highest tertile of exhaled CO was associated with lower total cerebral brain volumes (TCBV), higher white matter hyperintensity volumes (WMHV), and greater prevalence of silent cerebral infarcts (p &lt;0.05 for all). The results for TCBV and WMHV were consistent after removing smokers from the sample, and the association with WMHV persisted after multivariable adjustment (p=0.04). In prospective analyses (mean follow-up 12.9 years), higher exhaled CO was associated with 67% (second tertile) and 97% (top tertile) increased incidence of stroke/TIA relative to the first tertile that served as referent (p &lt;0.01 for both), Table. These results were consistent in nonsmokers, and were partially attenuated upon adjustment for vascular risk factors, but were maintained after adjusting for circulating biomarkers B-type natriuretic peptide and C-reactive protein, Table. Conclusion: In this large, community-based sample of individuals free of clinical stroke/TIA at baseline, higher exhaled CO was associated with a greater burden of subclinical cerebrovascular disease cross-sectionally, and with increased risk of stroke/TIA prospectively. Further investigation is necessary to explore the biological mechanisms linking CO with stroke.