Utility of multimodal longitudinal imaging data for dynamic prediction of cardiovascular and renal disease: the CARDIA study.

Background: Medical examinations contain repeatedly measured data from multiple visits, including imaging variables collected from different modalities. However, the utility of such data for the prediction of time-to-event is unknown, and only a fraction of the data is typically used for risk prediction. We hypothesized that multimodal longitudinal imaging data could improve dynamic disease prognosis of cardiovascular and renal disease (CVRD). Methods: In a multi-centered cohort of 5,114 CARDIA participants, we included 166 longitudinal imaging variables from five imaging modalities: Echocardiography (Echo), Cardiac and Abdominal Computed Tomography (CT), Dual-Energy x-ray Absorptiometry (DEXA), Brain Magnetic Resonance Imaging (MRI) collected from young adulthood to mid-life over 30 years (1985-2016) to perform dynamic survival analysis of CVRD events using machine learning dynamic survival analysis (Dynamic-DeepHit, LTRCforest, and Extended Cox for Time-varying Covariates). Risk probabilities were continuously updated as new data were collected. Model performance was assessed using integrated AUC and C-index and compared to traditional risk factors. Results: Longitudinal imaging data, even when being irregularly collected with high missing rates, improved CVRD dynamic prediction (0.03 in integrated AUC, up to 0.05 in C-index compared to traditional risk factors; best model's C-index = 0.80-0.83 up to 20 years from baseline) from young adulthood followed up to midlife. Among imaging variables, Echo and CT variables contributed significantly to improved risk estimation. Echo measured in early adulthood predicted midlife CVRD risks almost as well as Echo measured 10-15 years later (0.01 C-index difference). The most recent CT exam provided the most accurate prediction for short-term risk estimation. Brain MRI markers provided additional information from cardiac Echo and CT variables that led to a slightly improved prediction. Conclusions: Longitudinal multimodal imaging data readily collected from follow-up exams can improve CVRD dynamic prediction. Echocardiography measured early can provide a good long-term risk estimation, while CT/calcium scoring variables carry atherosclerotic signatures that benefit more immediate risk assessment starting in middle-age.

Multivariate longitudinal data for survival analysis of cardiovascular event prediction in young adults: insights from a comparative explainable study.

BACKGROUND: Multivariate longitudinal data are under-utilized for survival analysis compared to cross-sectional data (CS - data collected once across cohort). Particularly in cardiovascular risk prediction, despite available methods of longitudinal data analysis, the value of longitudinal information has not been established in terms of improved predictive accuracy and clinical applicability. METHODS: We investigated the value of longitudinal data over and above the use of cross-sectional data via 6 distinct modeling strategies from statistics, machine learning, and deep learning that incorporate repeated measures for survival analysis of the time-to-cardiovascular event in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. We then examined and compared the use of model-specific interpretability methods (Random Survival Forest Variable Importance) and model-agnostic methods (SHapley Additive exPlanation (SHAP) and Temporal Importance Model Explanation (TIME)) in cardiovascular risk prediction using the top-performing models. RESULTS: In a cohort of 3539 participants, longitudinal information from 35 variables that were repeatedly collected in 6 exam visits over 15 years improved subsequent long-term (17 years after) risk prediction by up to 8.3% in C-index compared to using baseline data (0.78 vs. 0.72), and up to approximately 4% compared to using the last observed CS data (0.75). Time-varying AUC was also higher in models using longitudinal data (0.86-0.87 at 5 years, 0.79-0.81 at 10 years) than using baseline or last observed CS data (0.80-0.86 at 5 years, 0.73-0.77 at 10 years). Comparative model interpretability analysis revealed the impact of longitudinal variables on model prediction on both the individual and global scales among different modeling strategies, as well as identifying the best time windows and best timing within that window for event prediction. The best strategy to incorporate longitudinal data for accuracy was time series massive feature extraction, and the easiest interpretable strategy was trajectory clustering. CONCLUSION: Our analysis demonstrates the added value of longitudinal data in predictive accuracy and epidemiological utility in cardiovascular risk survival analysis in young adults via a unified, scalable framework that compares model performance and explainability. The framework can be extended to a larger number of variables and other longitudinal modeling methods. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00005130, Registration Date: 26/05/2000.

The association of age at natural menopause with pre- to postmenopausal changes in left ventricular structure and function: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

OBJECTIVE: The association between menopause and incident cardiovascular disease (CVD) is controversial. We evaluated the relationships of estrogen deficiency (ovarian reproductive aging) assessed by age at natural menopause (ANM), chronological aging, and antecedent CVD risk factors (biological aging) with left ventricular (LV) structure and function among women transitioning from pre- to postmenopause. METHODS: We studied 771 premenopausal women (37% Black) from the Coronary Artery Risk Development in Young Adults Study with echocardiographic data in 1990 to 1991 (mean age: 32 y) who later reached natural menopause by 2015 to 2016 and had repeated echocardiographic measurements. Linear regression models were used to evaluate the association of ANM with parameters of LV structure and function. RESULTS: Mean ANM was 50 (± 3.8) years and the average time from ANM to the last echocardiograph was 7 years. In cross-sectional analyses, a 1-year increase in ANM was significantly associated with lower postmenopausal LV mass (LVM), LVM indexed to body surface area, LV mass-to-volume ratio, and relative wall thickness. In age-adjusted longitudinal analyses, higher ANM was inversely associated with pre- to postmenopausal changes in LVM (ß = -0.97; 95% CI: -1.81 to -0.13, P = 0.024) and LVM indexed (ß = -0.48; 95% CI: -0.89 to -0.07, P = 0.021). Controlling for baseline LV structure parameters and traditional CVD risk factors attenuated these associations. Further adjustment for hormone therapy uses did not alter these results. CONCLUSION: In this study, premenopausal CVD risk factors attenuated the association of ANM with changes in LV structure parameters. These data suggest that premenopausal CVD risk factors may predispose women to elevated future CVD risk more than ovarian aging.

Long-term cumulative blood pressure in young adults and incident heart failure, coronary heart disease, stroke, and cardiovascular disease: The CARDIA study.

AIMS: Cumulative blood pressure (BP) is a measure that incorporates the severity and duration of BP exposure. The prognostic significance of cumulative BP in young adults for cardiovascular diseases (CVDs) in comparison to BP severity alone is, however, unclear. METHODS AND RESULTS: We investigated 3667 Coronary Artery Risk Development in Young Adults participants who attended six visits over 15 years (year-0 (1985-1986), year-2, year-5, year-7, year-l0, and year-15 exams). Cumulative BP was calculated as the area under the curve (mmHg × years) from year 0 through year 15. Cox models assessed the association between cumulative BP (year 0 through year 15), current BP (year 15), and BP change (year 0 and year 15) and CVD outcomes. Mean (standard deviation) age at year 15 was 40.2 (3.6) years, 44.1% were men, and 44.1% were African-American. Over a median follow-up of 16 years, there were 47 heart failure (HF), 103 coronary heart disease (CHD), 71 stroke, and 191 CVD events. Cumulative systolic BP (SBP) was associated with HF (hazard ratio (HR) = 2.14 (1.58-2.90)), CHD (HR = 1.49 (1.19-1.87)), stroke (HR = 1.81 (1.38-2.37)), and CVD (HR = 1.73 (1.47-2.05)). For CVD, the C-statistic for SBP (year 15) was 0.69 (0.65-0.73) and change in C-statistic with the inclusion of SBP change and cumulative SBP was 0.60 (0.56-0.65) and 0.72 (0.69-0.76), respectively. For CVD, using year-15 SBP as a reference, the net reclassification index (NRI) for cumulative SBP was 0.40 (p < 0.0001) and the NRI for SBP change was 0.22 (p = 0.001). CONCLUSIONS: Cumulative BP in young adults was associated with the subsequent risk of HF, CHD, stroke, and CVD. Cumulative BP provided incremental prognostic value and improved risk reclassification for CVD, when compared to single BP assessments or changes in BP.

Long-Term Blood Pressure Variability in Young Adulthood and Coronary Artery Calcium and Carotid Intima-Media Thickness in Midlife: The CARDIA Study.

Recent evidence links long-term (visit-to-visit) blood pressure (BP) variability to the risk of cardiovascular disease, independent of mean BP levels. Potential associations between long-term BP variability and cardiovascular disease risk may be reflected in early life course alterations in coronary artery calcium (CAC) and carotid intima-media thickness. We evaluated 2482 CARDIA study (Coronary Artery Risk Development in Young Adults) participants (mean [SD] age at the year 20 exam [2005-2006] was 45.4 [3.6] years, 43.2% men, and 41.3% black). We included participants with BP assessments across 20-years (year 0, 2, 5, 7, 10, 15, 20 exams) and carotid intima-media thickness and CAC data at the year 20 exam. BP variability was assessed using variability independent of the mean and SD. Adjusted multivariable linear or logistic regression models (as appropriate) were used to assess associations between long-term BP variability measures and carotid intima-media thickness. and CAC (ln [CAC+1] and prevalent CAC). Long-term systolic BP variability independent of the mean (per 1 SD) was positively associated with carotid intima-media thickness (ß=10 µm, SE=3, P=0.002). Similarly, long-term diastolic BP variability independent of the mean was associated with carotid intima-media thickness (ß=10 µm, SE (3), P=0.001). Long-term BP variability was not associated with either ln [CAC+1] or prevalent CAC. Long-term systolic and diastolic BP variability across early adulthood was positively associated with modest adverse midlife alterations in carotid intima-media thickness but not to CAC. Our findings provide further insights into pathophysiologic mechanisms that link long-term BP variability to cardiovascular disease.

Coffee and tea consumption in the early adult lifespan and left ventricular function in middle age: the CARDIA study.

AIMS: The long-term impact of coffee or tea consumption on subclinical left ventricular (LV) systolic or diastolic function has not been previously studied. We examined the association between coffee or tea consumption beginning in early adulthood and cardiac function in midlife. METHODS AND RESULTS: We investigated 2735 Coronary Artery Risk Development in Young Adults (CARDIA) study participants with long-term total caffeine intake, coffee, and tea consumption data from three visits over a 20 year interval and available echocardiography indices at the CARDIA Year-25 exam (2010-2011). Linear regression models were used to assess the association between caffeine intake, tea, and coffee consumption (independent variables) and echocardiography outcomes [LV mass, left atrial volume, and global longitudinal strain (GLS), LV ejection fraction (LVEF), and transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity (E/e´)]. Models were adjusted for standard cardiovascular risk factors, socioeconomic status, physical activity, alcohol use, and dietary factors (calorie intake, whole and refined grain intake, and fruit and vegetable consumption). Mean (standard deviation) age was 25.2 (3.5) years at the CARDIA Year-0 exam (1985-1986), 57.4% were women, and 41.9% were African-American. In adjusted multivariable linear regression models assessing the relationship between coffee consumption and GLS, beta coefficients when comparing coffee drinkers of <1, 1-2, 3-4, and >4 cups/day with non-coffee drinkers were ß = -0.30%, P < 0.05; ß = -0.35%, P < 0.05; ß = -0.32%, P < 0.05; ß = -0.40%, P > 0.05; respectively (more negative values implies better systolic function). In adjusted multivariable linear regression models assessing the relationship between coffee consumption and E/e´, beta coefficients when comparing coffee drinkers of <1, 1-2, 3-4, and >4 cups/day with non-coffee drinkers were ß = -0.29, P < 0.05; ß = -0.38, P < 0.01; ß = -0.20, P > .05; and ß = -0.37, P > 0.05, respectively (more negative values implies better diastolic function). High daily coffee consumption (>4 cups/day) was associated with worse LVEF (ß = -1.69, P < 0.05). There were no associations between either tea drinking or total caffeine intake and cardiac function (P > 0.05 for all). CONCLUSIONS: Low-to-moderate daily coffee consumption from early adulthood to middle age was associated with better LV systolic and diastolic function in midlife. High daily coffee consumption (>4cups/day) was associated with worse LV function. There was no association between caffeine or tea intake and cardiac function.

Association Between Visit-to-Visit Blood Pressure Variability in Early Adulthood and Myocardial Structure and Function in Later Life.

Importance: Long-term blood pressure (BP) variability has emerged as a reproducible measure that is associated with heart failure independent of systemic BP. Visit-to-visit BP variability may be associated with the risk of heart failure early in the life course and thus may be reflected in subclinical alterations in cardiac structure and function. Objective: To evaluate the association between visit-to-visit BP variability in early adulthood and myocardial structure and function in middle age. Design, Setting, and Participants: This cohort study used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a community-based cohort study of 5115 participants aged 18 to 30 years at baseline (year 0; March 25, 1985, to June 7, 1986) and followed up over a 30-year interval. A total of 2400 CARDIA study participants underwent evaluation at 4 field sites (Birmingham, Alabama; Oakland, California; Chicago, Illinois; and Minneapolis, Minnesota). Blood pressure was measured at 8 visits over a 25-year interval and participants received echocardiograms at year 25 (June 1, 2010, to August 31, 2011). Data analysis was conducted from June 7, 1986, to August 31, 2011. Exposures: Visit-to-visit systolic and diastolic BP variability measures included SD, average real variability, and variability independent of the mean. Main Outcomes and Measures: Echocardiographic indices of myocardial structure, systolic function, and diastolic function at the year 25 examination. Results: Of the 2400 participants, 1024 were men (42.7%) and 976 were African American (40.7%); mean (SD) age at the year 25 examination was 50.4 (3.6) years. Per 1-SD increment, greater visit-to-visit systolic BP variability independent of the mean was associated with higher left-ventricular (LV) mass index (ß [SE], 2.66 [0.4] g/m2, P < .001), worse diastolic function (early peak diastolic mitral annular velocity [é]) (ß [SE], -0.40 [0.1] cm/s, P < .001), higher LV filling pressures (mitral inflow velocity to early diastolic mitral annular velocity [E/é]) ß [SE], 0.37 [0.1] cm/s, P < .001), and worse global longitudinal strain (ß [SE], 0.17 [0.1], P = .002). Similarly, greater visit-to-visit diastolic BP variability was associated with higher LV mass index (ß [SE], 3.21 [0.5] g/m2, P < .001), worse diastolic function (é: ß [SE], -0.24 [0.1] cm/s [P < .001]; E/é: ß [SE], 0.23 [0.1] cm/s [P < .001]), and worse global longitudinal strain (ß [SE], 0.13 [0.1], P = .02). The findings remained consistent when other BP variability measures were used (SD and average real variability). Conclusions and Relevance: In this cohort study using data from the CARDIA study, greater visit-to-visit systolic and diastolic BP variability have been associated with adverse alterations in cardiac structure as well as systolic and diastolic function independent of mean BP levels.

Association of smoking and right ventricular function in middle age: CARDIA study.

Objective: To evaluate the association of cigarette smoking and right ventricular (RV) systolic and diastolic functions in a population-based cohort of individuals at middle age. Methods: This cross-sectional study included participants who answered the smoking questionnaire and underwent echocardiography at the Coronary Artery Risk Development in Young Adulthood year 25 examination. RV systolic function was assessed by echocardiographic-derived tricuspid annular plane systolic excursion (TAPSE) and by right ventricular peak systolic velocity (RVS'), while RV diastolic function was evaluated by early right ventricular tissue velocity (RVE'). Multivariable linear regression models assessed the relationship of smoking with RV function, adjusting for age, sex, race, body mass index, systolic blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, diabetes mellitus, alcohol consumption, pulmonary function, left ventricular systolic and diastolic function and coronary artery calcium score. Results: A total of 3424 participants were included. The mean age was 50±4 years; 57% were female; and 53% were black. There were 2106 (61%) never smokers, 750 (22%) former smokers and 589 (17%) current smokers. In the multivariable analysis, current smokers had significantly lower TAPSE (ß=-0.082, SE=0.031, p=0.008), RVS' (ß=-0.343, SE=0.156, p=0.028) and RVE' (ß=-0.715, SE=0.195, p<0.001) compared with never smokers. Former smokers had a significantly lower RVE' compared with never smokers (ß=-0.414, SE=0.162, p=0.011), whereas no significant difference in RV systolic function was found between former smokers and never smokers. Conclusions: In a large multicenter community-based biracial cohort of middle-aged individuals, smoking was independently related to both worse RV systolic and diastolic functions.

Temporal Changes in Resting Heart Rate, Left Ventricular Dysfunction, Heart Failure and Cardiovascular Disease: CARDIA Study.

BACKGROUND: The prognostic significance of temporal changes in resting heart rate in young adults for premature heart failure and cardiovascular disease is unclear. We investigated the association between temporal changes in resting heart rate in young adults and early adult risk factors, subsequent cardiac function, and the risk of heart failure and cardiovascular by middle age. METHODS: We examined 4343 Coronary Artery Risk Development in Young Adults (CARDIA) study participants (mean [SD] age was 29.9 [3.6] years at the CARDIA Year-5 examination [1990-1991], 49% of participants were men, and 45% were African-American). Adjusted linear regression models were used to assess the association between temporal changes in resting heart rate, early life cardiovascular disease risk factors, and midlife cardiac function. Cox proportional hazard regression models were used to relate temporal changes in resting heart rate to heart failure and cardiovascular disease. Outcomes were followed up until August 31, 2017. RESULTS: Higher alcohol consumption (ß = 0.03, P <0.001), lower physical activity (ß = 0.002, P = 001), smoking (ß = 1.58, P <0.001), men (P <0.001), African Americans (P <0.001), impaired left ventricular relaxation (e´,ß = -0.13, P = 0.002), and worse diastolic function (E/e´, ß = 0.1, P = 0.01) were associated with longitudinal increases in resting heart rate. We observed 268 cardiovascular disease and 74 heart failure events over a median of 26 years. In Cox models, baseline and temporal changes in resting heart rate were associated with higher risk of heart failure (hazard ratio [HR] =1.37 95% confidence interval [CI] [1.05-1.79] and HR = 1.38 95% CI [1.02-1.86]) and a higher risk cardiovascular disease (HR = 1.23 95% CI [1.07-1.42] and HR = 1.23 95% CI [1.05-1.44]). CONCLUSIONS: Baseline and temporal changes in resting heart rate in young adults were associated with incident heart failure and cardiovascular disease by midlife. Contributory factors were associations between temporal increases in resting heart rate and early adult risk factors and subsequent cardiac dysfunction.

Pulmonary Artery Acceleration Time in Young Adulthood and Cardiovascular Outcomes Later in Life: The Coronary Artery Risk Development in Young Adults Study.

BACKGROUND: Lower pulmonary artery acceleration time (PAcT) is correlated with higher pulmonary artery pressure. The aim of this study was to test the hypothesis that PAcT measured in young adulthood would be associated with future cardiovascular outcomes. METHODS: In the Coronary Artery Risk Development in Young Adults year 5 examination (1990-1991), PAcT was measured as the time interval from onset to peak flow velocity at the pulmonary valve annulus on Doppler echocardiography. The primary outcome was a composite of fatal or nonfatal cardiovascular disease events: myocardial infarction, non-myocardial infarction acute coronary syndrome, coronary revascularization, congestive heart failure, stroke, transient ischemic attack, carotid artery disease, and peripheral arterial disease. RESULTS: PAcT was obtained in 4,171 participants (mean age, 30 ± 4 years, 55% women, 51% white). PAcT groups obtained using linear spline methodology were as follows: group I, PAcT ≥ 196 msec (n = 122); group II, PAcT < 196 and ≥115 msec (n = 3,195); and group III, PAcT < 115 msec (n = 854). During follow-up (median, 24.9 years), the primary outcome occurred in 216 participants (5.2%); 66 of 854 (7.7%) of those with PAcT < 115 msec, 149 of 3,195 (4.7%) of those with intermediate PAcT level, and one of 122 (0.8%) of those with PAcT ≥ 196 msec. In a fully adjusted model, the lowest and intermediate PAcT groups had hazard ratios of 8.3 (95% CI, 1.1-62.1; P = .04) and 6.8 (95% CI, 0.9-50.5; P = .06), respectively, in comparison with the highest PAcT group. CONCLUSIONS: PAcT is useful for better identifying young adults at higher risk for cardiovascular events, who may benefit from a strict control of modifiable cardiovascular risk factors.

Coronary Artery Calcium From Early Adulthood to Middle Age and Left Ventricular Structure and Function.

Background The relationship of coronary artery calcium (CAC) with adverse cardiac remodeling is not well established. We aimed to study the association of CAC in middle age and change in CAC from early adulthood to middle age with left ventricular (LV) function. Methods CAC score was measured by computed tomography at CARDIA study (Coronary Artery Risk Development in Young Adults) year-15 examination and at year-25 examination (Y25) in 3043 and 3189 participants, respectively. CAC score was assessed as a continuous variable and log-transformed to account for nonlinearity. Change in CAC from year-15 examination to Y25 was evaluated as the absolute difference of log-transformed CAC from year-15 examination to Y25. LV structure and function were evaluated by echocardiography at Y25. Results At Y25, mean age was 50.1±3.6 years, 56.6% women, 52.4% black. In the multivariable analysis at Y25, higher CAC was related to higher LV mass (ß=1.218; adjusted P=0.007), higher LV end-diastolic volume (ß=0.811; adjusted P=0.007), higher LV end-systolic volume (ß=0.350; adjusted P=0.048), higher left atrial volume (ß=0.214; adjusted P=0.009), and higher E/e' ratio (ß=0.059; adjusted P=0.014). CAC was measured at both year-15 examination and Y25 in 2449 individuals. Higher change in CAC score during follow-up was independently related to higher LV mass index in blacks (ß=4.789; adjusted P<0.001), but not in whites (ß=1.051; adjusted P=0.283). Conclusions Higher CAC in middle age is associated with higher LV mass and volumes and worse LV diastolic function. Being free of CAC from young adulthood to middle age correlates to better LV function at middle age. Higher change in CAC score during follow-up is independently related to higher LV mass index in blacks.

Left ventricular global function index predicts incident heart failure and cardiovascular disease in young adults: the coronary artery risk development in young adults (CARDIA) study.

AIMS: Left ventricular (LV) ejection fraction (LVEF) is an extensively utilized marker of LV function that is often interpreted without recourse to alterations in LV geometry and hypertrophy. LV global function index (LVGFI) is a novel marker that incorporates LV structure in the assessment of LV cardiac performance. We evaluated the prognostic utility of LVGFI from young adulthood into middle age for incident heart failure (HF) and cardiovascular disease (CVD) in comparison to LVEF. METHODS AND RESULTS: Included were 4107 CARDIA participants with echocardiograms in Year-5 (1990-1991). LVGFI was defined as LV stroke volume/LV global volume*100, where LV global volume was the sum of the LV mean cavity volume ((LV end-diastolic volume + LV end-systolic volume)/2) and myocardial volume (LV mass/density). Adjusted Cox proportional hazard models were utilized to predict incident HF and CVD outcomes. Mean age of participants was 29.8 ± 3.7 years, 55% female, and 48.7% black. Higher body mass index [beta coefficient (B) = -0.11 standard error (SE) = 0.02, P < 0.001], higher blood pressure (B = -0.04, SE = 0.01, P < 0.01), smoking (B = -0.82, SE = 0.22, P < 0.001), male sex (P < 0.001), and black race (P < 0.001) were associated with worse LVGFI. A total of 207 incident CVD events were observed over the course of 98 035 person-years at risk. Higher LVGFI was associated with HF, hazard ratio (HR) = 0.70, 95% confidence interval (CI) (0.54-0.91), hard CVD HR = 0.83, 95% CI (0.71-0.96), and all CVD HR = 0.83, 95% CI (0.72-0.96). For HF outcomes, Harrell's C-statistic for LVGFI (0.80) was greater than LVEF (0.66). CONCLUSION: LVGFI is a strong, independent predictor of incident HF and CVD that provides incremental prognostic value compared with LVEF. Male sex, black race, obesity, hypertension, and smoking are associated with worse LVGFI in the early adult lifespan.

Association Between Inflammatory Markers and Myocardial Fibrosis.

Inflammation promotes adverse ventricular remodeling. T1 mapping has been used to noninvasively assess interstitial myocardial fibrosis. We examined the association of baseline markers of systemic inflammation with interstitial myocardial fibrosis measured by extracellular volume fraction (ECV) and native T1 mapping at 10-year follow-up in the MESA (Multi-Ethnic Study of Atherosclerosis). Seven hundred seventy-two participants had complete baseline data and underwent cardiac magnetic resonance imaging. All analyses were stratified by sex. Multivariable linear regression models were constructed to assess the associations of baseline CRP (C-reactive protein), IL (interleukin)-6, and fibrinogen with native T1 time and ECV. Longer native T1 times and higher percentages of ECV represent increasing myocardial fibrosis. A 1-SD increment of log-transformed IL-6 levels was associated with 0.4% higher ECV in men (ß=0.4; P=0.05). CRP and fibrinogen were not associated to ECV. A 1-SD increment in the log-transformed CRP levels was associated with 4.9 ms higher native T1 (ß=4.9; P=0.03). In women, the inflammatory markers did not demonstrate association with native T1 nor ECV. Higher IL-6 and CRP levels are associated with increased interstitial myocardial fibrosis assessed by cardiac magnetic resonance in men. However, no inflammatory markers were associated to myocardial fibrosis in women.

Association of Patterns of Change in Adiposity With Diastolic Function and Systolic Myocardial Mechanics From Early Adulthood to Middle Age: The Coronary Artery Risk Development in Young Adults Study.

BACKGROUND: The aim of this study was to determine whether long-term patterns of change in adiposity throughout young adulthood are associated with systolic and diastolic function in midlife. METHODS: Participants in the Coronary Artery Risk Development in Young Adults study, a multicenter, population-based cohort, underwent repeated anthropometric assessment (body mass index [BMI], waist circumference, and waist-to-hip ratio) from examination years 0 to 25. At year 25, longitudinal, circumferential, and radial strain and tissue Doppler velocities were assessed by echocardiography. Group-based trajectory modeling was used to identify 25-year trajectories of change in anthropometric measures and to examine associations between trajectories of adiposity change and indices of cardiac mechanics. RESULTS: Among 3,310 participants, four distinct trajectories of BMI change were identified: stable BMI (36% of the cohort; mean ΔBMI, 1.6 kg/m2), mild increase (40%; mean ΔBMI, 6.0 kg/m2), moderate increase (18%; mean ΔBMI, 10.8 kg/m2), and major increase (6%; mean ΔBMI, 15.5 kg/m2). Trajectories of greater BMI increase were associated with lower adjusted e' velocity and higher E/e' ratio compared with the stable BMI group, independent of year 0 or year 25 BMI. Participants in increasing BMI trajectory groups compared with the stable BMI group had lower absolute longitudinal strain and greater odds of diastolic dysfunction, independent of year 0 BMI but not year 25 BMI. Similar patterns were observed for change in waist circumference and waist-to-hip ratio trajectory groups. CONCLUSIONS: Steeper trajectories of BMI increase from young adulthood to middle age, a vulnerable period for weight gain, are independently associated with lower e' velocity and higher E/e' ratio, but not systolic dysfunction, in midlife.

Cumulative blood pressure from early adulthood to middle age is associated with left atrial remodelling and subclinical dysfunction assessed by three-dimensional echocardiography: a prospective post hoc analysis from the coronary artery risk development in young adults study.

Aims: To evaluate the association of cumulative blood pressure (BP) from young adulthood to middle age with left atrial (LA) structure/function as assessed by three-dimensional echocardiography (3DE) in a large longitudinal bi-racial population study. Methods and results: We conducted a prospective post hoc analysis of individuals enrolled at the Coronary Artery Risk Development in Young Adults, which is a multi-centre bi-racial cohort with 30 years of follow-up. Cumulative systolic and diastolic BP levels were defined by summing the product of average millimetres of mercury and the years between each two consecutive clinic visits over 30 years of follow-up. Multivariable linear regression analyses were used to assess the relationship between cumulative systolic and diastolic BP with 3DE LA structure and function, adjusting for demographics and traditional cardiovascular risk factors. A total of 1033 participants were included, mean age was 55.4 ± 3.5 years, 55.2% women, 43.9% blacks. Cumulative systolic BP had stronger correlations than cumulative diastolic BP. Higher cumulative systolic BP was independently associated with higher 3D LA volumes: maximum (ß = 1.74, P = 0.004), pre-atrial contraction (ß = 1.87, P < 0.001), minimum (ß = 0.76, P = 0.04), total emptying (ß = 0.98, P = 0.006), active emptying (ß = 1.12, P < 0.001), and lower magnitude 3D LA early diastolic strain rate (ß = 0.05, P = 0.02). Higher cumulative diastolic BP was independently associated with higher 3D LA active emptying volume (ß = 0.66, P = 0.002), lower magnitude 3D LA early diastolic strain rate (ß = 0.05, P = 0.004), and higher magnitude 3D LA late diastolic strain rate (ß = -0.04, P = 0.05). Conclusion: Higher cumulative BP from early adulthood throughout middle age was associated with adverse LA remodelling evaluated by 3D echocardiography.

Association of Aortic Root Dilation from Early Adulthood to Middle Age with Cardiac Structure and Function: The CARDIA Study.

BACKGROUND: The human aorta dilates with advancing age. However, the association between progressive aortic dilation with aging and cardiac remodeling has not been established in studies of community-dwelling adults. The aim of this study was to test the hypothesis that there would be a relationship between aortic size increase over the early adult life span with left ventricular (LV) structural remodeling and subclinical LV dysfunction in middle age, even in the absence of overt cardiovascular and valvular disease. METHODS: Included were Coronary Artery Risk Development in Young Adults study participants (N = 2,933) aged 23 to 35 years with available transthoracic echocardiographic measurements during 20 years of follow-up. Multivariate linear regression models assessed sex-specific associations between 20-year change in aortic root diameter with LV structure and function. RESULTS: Larger aortic root diameter at 20-year follow-up was associated with greater LV mass (2.77 vs 2.18 g/mm in men and women, respectively, P < .001). In longitudinal analyses, increase in aortic root diameter over 20-year follow-up was associated with a greater 20-year increase in LV mass and ratio of LV mass to LV end-diastolic volume ratio in both sexes. In women but not in men, increased aortic root diameter over 20 years was associated with increased left atrial dimension, impaired E/E', and impaired early diastolic longitudinal and circumferential strain rates assessed by speckle-tracking echocardiography. CONCLUSIONS: Progressive increase in aortic root diameter from early adulthood to middle age was associated with increased LV mass and LV concentric remodeling in both sexes and impaired diastolic function predominantly in women.